c-peptide and Diabetic-Angiopathies

Recent research in nutritional control of aging suggests that cytosolic increases in the reduced form of nicotinamide adenine dinucleotide and decreasing nicotinamide adenine dinucleotide metabolism plays a central role in controlling the longevity gene products sirtuin 1 (SIRT1), adenosine monophosphate-activated protein kinase (AMPK) and forkhead box O3 (FOXO3). High nutrition conditions, such as the diabetic milieu, increase the ratio of reduced to oxidized forms of cytosolic nicotinamide adenine dinucleotide through cascades including the polyol pathway. This redox change is associated with insulin resistance and the development of diabetic complications, and might be counteracted by insulin C-peptide. My research and others' suggest that the SIRT1-liver kinase B1-AMPK cascade creates positive feedback through nicotinamide adenine dinucleotide synthesis to help cells cope with metabolic stress. SIRT1 and AMPK can upregulate liver kinase B1 and FOXO3, key factors that help residential stem cells cope with oxidative stress. FOXO3 directly changes epigenetics around transcription start sites, maintaining the health of stem cells. 'Diabetic memory' is likely a result of epigenetic changes caused by high nutritional conditions, which disturb the quiescent state of residential stem cells and impair tissue repair. This could be prevented by restoring SIRT1-AMPK positive feedback through activating FOXO3.

Topics: Aging; AMP-Activated Protein Kinases; Animals; C-Peptide; Diabetes Complications; Diabetic Angiopathies; Disease Models, Animal; Epigenesis, Genetic; Feedback, Physiological; Forkhead Box Protein O3; Humans; Hypoxia; Insulin Resistance; NAD; Oxidation-Reduction; Oxidative Stress; Signal Transduction; Sirtuin 1

C-peptide is produced, processed, and secreted with insulin, and appears to exert separate but intimately related effects. In this review, we address the existence of the C-peptide receptor, the interaction between C-peptide and insulin, and the potential physiological significance of proinsulin C-peptide.

Topics: Animals; C-Peptide; Diabetic Angiopathies; Endothelium, Vascular; Humans; Insulin; Insulin Secretion; Insulin-Secreting Cells; Models, Biological; Receptors, G-Protein-Coupled; Signal Transduction

Lack of C-peptide, along with insulin, is the main feature of Type 1 diabetes mellitus (DM) and is also observed in progressive β-cell loss in later stage of Type 2 DM. Therapeutic approaches to hyperglycaemic control have been ineffective in preventing diabetic vasculopathy, and alternative therapeutic strategies are necessary to target both hyperglycaemia and diabetic complications. End-stage organ failure in DM seems to develop primarily due to vascular dysfunction and damage, leading to two types of organ-specific diseases, such as micro- and macrovascular complications. Numerous studies in diabetic patients and animals demonstrate that C-peptide treatment alone or in combination with insulin has physiological functions and might be beneficial in preventing diabetic complications. Current evidence suggests that C-peptide replacement therapy might prevent and ameliorate diabetic vasculopathy and organ-specific complications through conservation of vascular function, as well as prevention of endothelial cell death, microvascular permeability, vascular inflammation, and neointima formation. In this review, we describe recent advances on the beneficial role of C-peptide replacement therapy for preventing diabetic complications, such as retinopathy, nephropathy, neuropathy, impaired wound healing, and inflammation, and further discuss potential beneficial effects of combined C-peptide and insulin supplement therapy to control hyperglycaemia and to prevent organ-specific complications.

Topics: Animals; C-Peptide; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Humans; Hypoglycemic Agents; Signal Transduction; Treatment Outcome

Hyperglycemia is considered to be the major cause of microvascular complications of diabetes. Growing evidence highlights the importance of hyperglycemia-mediated inflammation in the initiation and progression of microvascular complications in type 1 diabetes. We hypothesize that lack of proinsulin C-peptide and lack of its anti-inflammatory properties contribute to the development of microvascular complications. Evidence gathered over the past 20 years shows that C-peptide is a biologically active peptide in its own right. It has been shown to reduce formation of reactive oxygen species and nuclear factor-κB activation induced by hyperglycemia, resulting in inhibition of cytokine, chemokine and cell adhesion molecule formation as well as reduced apoptotic activity. In addition, C-peptide stimulates and induces the expression of both Na⁺, K⁺-ATPase and endothelial nitric oxide synthase. Animal studies and small-scale clinical trials in type 1 diabetes patients suggest that C-peptide replacement combined with regular insulin therapy exerts beneficial effects on kidney and nerve dysfunction. Further clinical trials in patients with microvascular complications including measurements of inflammatory markers are warranted to explore the clinical significance of the aforementioned, previously unrecognized, C-peptide effects.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; C-Peptide; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Endothelium, Vascular; Humans; Microvessels

The incidence and prevalence of diabetes are increasing worldwide. According to the International Diabetes Federation, more than 55 million people in the European region have diabetes, and this number is expected to rise to 64 million in 2030, with most of the cases being due to type 2 diabetes. Diabetes is associated with potentially serious microvascular and macrovascular complications such as nephropathy, neuropathy, and retinopathy as well as coronary artery disease. The pathophysiological mechanism behind this phenomenon is complex. In recent years the impact of proinsulin C-peptide in the development of vascular disease has been highlighted, but it displays differential function in type 1 and type 2 diabetes. In type 1 diabetes, which is characterized by a lack of insulin and C-peptide, supplementation of C-peptide has been shown to improve microvascular complications. In type 2 diabetes, however, C-peptide levels are increased above normal levels and correlate with the occurrence of macrovascular complications and cardiovascular deaths. This review focuses on the impact of C-peptide in the atherogenic process.

Topics: Animals; Atherosclerosis; C-Peptide; Diabetic Angiopathies; Disease Models, Animal; Endothelium, Vascular; Humans; Hyperglycemia; Inflammation; NF-kappa B

C-peptide is secreted from proinsulin and over the recent decade is considered as an active peptide that leads to different capillary actions and macrovascular complications in patients with type 2 diabetes mellitus. Results of the recent researches showed the C-peptide uptake in the blood vessel walls, in the juxtaglomerular apparatus of malpighian tuft, induction of local inflammation, proliferative effect on mesangial cell. The given effects showed an atherogenic role of C-peptide. Authors consider C-peptide as a possible predicator of cardiovascular complications and mortality in patients with type 2 diabetes mellitus and without diabetes.

Topics: Animals; C-Peptide; Capillaries; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Humans

Patients with insulin resistance and early type 2 diabetes exhibit an increased propensity to develop a diffuse and extensive pattern of arteriosclerosis. Diabetic subjects show a remarkable increase in vascular complications, including myocardial infarction and strokes. The accelerated atherosclerosis in these patients is likely to be multifactorial. In this review, we focus on the advanced glycation end product (AGE)-receptor for AGE (RAGE) axis and the role of C-peptide as a mediator of lesion development. AGEs are proteins or lipids that become glycated after exposure to sugars. By engaging the RAGEs, AGEs induce the expression of proinflammatory mediators in various vascular cell types and are involved in a variety of microvascular and macrovascular complications. In animal models, interruption of the AGE-RAGE interaction reduces lesion size and plaque development and RAGE deficiency in a RAGE(-/-)/apolipoprotein E(-/-) double knockout mouse attenuates the development of atherosclerosis in diabetes. On the other side, patients with type 2 diabetes show increased levels of C-peptide and over the last years various groups examined the effect of C-peptide in vascular cells as well as its potential role in lesion development. Recent data suggest that the proinsulin cleavage product C-peptide could play a causal role in atherogenesis by promoting monocyte and CD4-positive lymphocyte recruitment in early arteriosclerotic lesions and by inducing the proliferation of vascular smooth muscle cells. The following review will summarize these two pathophysiological aspects and discuss on the one hand the potential role of the activated AGE-RAGE axis in diabetes-accelerated atherogenesis and on the other hand the role of C-peptide as a mediator in lesion development in patients with type 2 diabetes.

Topics: Animals; Apolipoproteins E; Atherosclerosis; C-Peptide; CD4-Positive T-Lymphocytes; Cell Proliferation; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Gene Expression Regulation; Glycation End Products, Advanced; Humans; Inflammation Mediators; Mice; Mice, Knockout; Mitogen-Activated Protein Kinases; Monocytes; Myocardial Infarction; Myocytes, Smooth Muscle; Receptor for Advanced Glycation End Products; Stroke

During the recent years, the role of C-peptide, released from the pancreatic beta cell, in regulating microvascular blood flow, has received increasing attention. In type 1 diabetic patients, intravenous application of C-peptide in physiological concentrations was shown to increase microvascular blood flow, and to improve microvascular endothelial function and the endothelial release of NO. C-peptide was shown to impact microvascular blood flow by several interactive pathways, like stimulating Na(+)K(+)ATPase or the endothelial release of NO. There is increasing evidence, that in patients with declining beta cell function, the lack of C-peptide secretion might play a putative role in the development of microvascular blood flow abnormalities, which go beyond the effects of declining insulin secretion or increased blood glucose levels.

Topics: Blood Flow Velocity; C-Peptide; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Endothelium, Vascular; Erythrocyte Deformability; Humans; Microcirculation; Nitric Oxide

Patients with insulin resistance and early type 2 diabetes exhibit an increased propensity to develop a diffuse and extensive pattern of arteriosclerosis. Various risk factors such as hypertension, dyslipidemia, and a proinflammatory and prothrombotic state contribute to atherogenesis in this high-risk population, but the pathophysiologic mechanisms leading to this characteristic pattern remain largely unexplored. Recent data suggest that the proinsulin cleavage product C-peptide could play a causal role in atherogenesis by promoting monocyte and CD4-positive lymphocyte recruitment in early arteriosclerotic lesions and by inducing the proliferation of vascular smooth muscle cells. The following review will summarize the effects of C-peptide in vascular cells and discuss the potential relevance of such C-peptide effects on atherogenesis in diabetic patients.

Topics: Atherosclerosis; C-Peptide; Diabetic Angiopathies; Humans; Insulin Resistance

Patients with insulin resistance and early type 2 diabetes exhibit an increased propensity to develop a diffuse and extensive pattern of arteriosclerosis. Typically, these patients show increased levels of C-peptide and over the last years various groups examined the effect of C-peptide in vascular cells as well as its potential role in lesion development. While some studies demonstrated beneficial effects of C-peptide, for example, by showing an inhibition of smooth muscle cell proliferation, others suggested proatherogenic mechanisms in patients with type 2 diabetes. Among them, C-peptide may facilitate the recruitment of inflammatory cells into early lesions and promote lesion progression by inducing smooth muscle cell proliferation. The following review will summarize the effects of C-peptide in vascular cells and discuss the potential role of C-peptide in atherogenesis in patients with type 2 diabetes.

Topics: Atherosclerosis; C-Peptide; Cell Division; Chemotaxis, Leukocyte; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Humans; Muscle, Smooth, Vascular

To evaluate the lipoprotein profiles, triglycerides and glycemia along with the abdominal fat to explore the risk factors associated with non-diabetic state to IGF, IGT and Type-2 diabetes in Canadian population.. We examined 780 subjects using the ADA and WHO criteria to classify them into groups based on (1) normal glucose tolerance with FBS <6.0 and 2hBS <7.0 mmol/l), (2) IFG; FPG > or =6.1 mmol/l but 2hBS >7.8-11.1 mmol/l; (3) combined IFG/IGT (FPG > or =7.0 mmol/l and 2hBS >11.1 mmol/l). We compared the three groups for glycemia, insulin secretion and insulin sensitivity based on their WHR, abdominal and visceral fat measurements.. The subjects with higher 2 hrs glucose levels 5.2 for NGT vs. 9.1 for IGT and 13.4 mmol/l for NIDDM, p<0.001, apo C-III level (12.8 (DM) vs. 8.9 mg/dl (normal), p<0.001), waist to hip ratio (0.91 (IGT) vs. 0.89 (Normal), p<0.01) and abdominal fat and were found to be highly insulin resistant.. The higher apolipoproteins levels, BMI and abdominal and visceral fat accompanied by poor glycemia were shown to be associated strongly with the metabolic abnormalities. These factors led to the worsening of insulin secretory dysfunction and insulin resistance and were strong predictors of diabetes.

Topics: Adipose Tissue; Atherosclerosis; Biomarkers; Blood Glucose; C-Peptide; Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus; Diabetic Angiopathies; Fatty Acids, Nonesterified; Glycated Hemoglobin; Humans; Insulin; Insulin Secretion; Metabolic Syndrome; Risk Factors; Triglycerides

Proinsulin connecting peptide (C-peptide) has been initially regarded as deprived of biological functions other than correct scaffolding of insulin. This was caused by the lack of evident effect of C-peptide administration to healthy subjects or animals. At present, in view of numerous studies concerning its structure, membrane binding and biological functions, C-peptide seems to constitute a crucial role in the pathogenesis of complications in diabetes mellitus type 1 (DM1). Patients who maintain high remnant insulin secretion (and therefore also of C-peptide) develop complications such as nephropathy, neuropathy and later microangiopathy with a milder clinical course. In this article we have covered molecular and cellular aspects of C-peptide functioning, such as: activation of protein kinase C, Na+,K+- ATP-ase, nitric oxide synthase, MAP and ERK 1/2 kinases, improvement of nerve conduction velocity and interactions with exogenous and endogenous insulin. We also outline the clinical consequences of deficiency of this underestimated peptide along with its potential therapeutical possibilities in the primary and secondary prevention of DM1 complications.

Topics: Amino Acid Sequence; Animals; C-Peptide; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Diabetic Nephropathies; Diabetic Neuropathies; Humans; Insulin; Proinsulin; Rats; Signal Transduction

Topics: Atherosclerosis; C-Peptide; Cardiovascular Diseases; Cell Proliferation; Diabetic Angiopathies; Humans; Hyperinsulinism; Insulin Resistance; Mitogens; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle

Topics: C-Peptide; Diabetes Complications; Diabetic Angiopathies; Diabetic Nephropathies; Diabetic Neuropathies; Humans

Diabetes mellitus is a heterogeneous disorder. About 80% of the patients with this disease are categorized as having non-insulin-dependent diabetes mellitus, a disorder resulting from varied degrees of insulin resistance and impaired insulin secretion; the causes for these abnormalities are unknown. The remaining 15 to 20% of patients have insulin-dependent diabetes mellitus, a disorder caused by the destruction of insulin-producing endocrine cells within the pancreas and currently considered to be the result of an autoimmune process. During the course of both types of diabetes mellitus, the so-called long-term complications of diabetes invariably occur to some extent in all patients. These complications include retinopathy, nephropathy, neuropathy, and premature atherosclerosis. The molecular basis for these complications is not completely understood, but recent evidence obtained from both experiments in animals and prospective clinical studies indicates that metabolic derangements associated with poor glycemic control are a major determinant of the frequency and severity of these complications. Such evidence is the rationale for current attempts to maintain near-normal glycemia in patients with diabetes mellitus.

Topics: Autoimmune Diseases; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Nephropathies; Diabetic Neuropathies; Diabetic Retinopathy; Diagnosis, Differential; Glucagon; Humans; Insulin; Insulin Resistance

Topics: Adolescent; Adult; Blood Glucose; C-Peptide; Delayed-Action Preparations; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Diabetic Retinopathy; Glycated Hemoglobin; Glycosuria; Humans; Hypoglycemia; Insulin; Insulin Infusion Systems; Insulin Secretion; Time Factors

Topics: Antibodies, Viral; Antigen-Antibody Complex; Autoantibodies; C-Peptide; Cross Reactions; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Diabetic Retinopathy; Enterovirus; HLA Antigens; Humans; Hyperthyroidism; Islets of Langerhans; Killer Cells, Natural; Receptors, Cell Surface; Risk; Thyroid Gland; Thyrotropin

Diabetes is associated with increased oxidative stress and atherosclerosis development. In the present study, we investigated the effects of pomegranate juice (PJ; which contains sugars and potent anti-oxidants) consumption by diabetic patients on blood diabetic parameters, and on oxidative stress in their serum and macrophages. Ten healthy subjects (controls) and 10 non-insulin dependent diabetes mellitus (NIDDM) patients who consumed PJ (50ml per day for 3 months) participated in the study. In the patients versus controls serum levels of lipid peroxides and thiobarbituric acid reactive substances (TBARS) were both increased, by 350% and 51%, respectively, whereas serum SH groups content and paraoxonase 1 (PON1) activity, were both decreased (by 23%). PJ consumption did not affect serum glucose, cholesterol and triglyceride levels, but it resulted in a significant reduction in serum lipid peroxides and TBARS levels by 56% and 28%, whereas serum SH groups and PON1 activity significantly increased by 12% and 24%, respectively. In the patients versus controls monocytes-derived macrophages (HMDM), we observed increased level of cellular peroxides (by 36%), and decreased glutathione content (by 64%). PJ consumption significantly reduced cellular peroxides (by 71%), and increased glutathione levels (by 141%) in the patients' HMDM. The patients' versus control HMDM took up oxidized LDL (Ox-LDL) at enhanced rate (by 37%) and PJ consumption significantly decreased the extent of Ox-LDL cellular uptake (by 39%). We thus conclude that PJ consumption by diabetic patients did not worsen the diabetic parameters, but rather resulted in anti-oxidative effects on serum and macrophages, which could contribute to attenuation of atherosclerosis development in these patients.

Topics: Adult; Aged; Antioxidants; Atherosclerosis; C-Peptide; Carbohydrates; Cells, Cultured; Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Flavonoids; Humans; Lipid Peroxidation; Lipoproteins, LDL; Lythraceae; Macrophages; Male; Middle Aged; Monocytes; Oxidative Stress; Phenols; Plant Extracts; Polyphenols; Triglycerides

To examine whether intensive glycemic control could decrease the frequency or severity of diabetic microvascular complications, we performed a prospective study of Japanese patients with non-insulin-dependent diabetes mellitus (NIDDM) treated with multiple insulin injection treatment. A total of 110 patients with NIDDM was randomly assigned to multiple insulin injection treatment group (MIT group) or to conventional insulin injection treatment group (CIT group). Fifty-five NIDDM patients who showed no retinopathy and urinary albumin excretions < 30 mg/24 h at the baseline were evaluated in the primary-prevention cohort, and the other 55 NIDDM patients who showed simple retinopathy and urinary albumin excretions < 300 mg/24 h were evaluated in the secondary-intervention cohort. The appearance and the progression of retinopathy, nephropathy and neuropathy were evaluated every 6 months over a 6-year period. The worsening of complications in this study was defined as an increase of 2 or more steps in the 19 stages of the modified ETDRS interim scale for retinopathy and an increase of one or more steps in 3 stages (normoalbuminuria, microalbuminuria and albuminuria) for nephropathy. The cumulative percentages of the development and the progression in retinopathy after 6 years were 7.7% for the MIT group and 32.0% for the CIT group in the primary-prevention cohort (P = 0.039), and 19.2% for MIT group and 44.0% for CIT group in the secondary-intervention cohort (P = 0.049). The cumulative percentages of the development and the progression in nephropathy after 6 years were 7.7% for the MIT group and 28.0% for the CIT group in the primary-prevention cohort (P = 0.032), and 11.5% and 32.0%, respectively, for the MIT and CIT groups in the secondary-intervention cohort (P = 0.044). In neurological tests after 6 years, MIT group showed significant improvement in the nerve conduction velocities, while the CIT group showed significant deterioration in the median nerve conduction velocities and vibration threshold. Although both postural hypotension and the coefficient of variation of R-R interval tended to improve in the MIT group, they deteriorated in the CIT group. In conclusion, intensive glycemic control by multiple insulin injection therapy can delay the onset and the progression of diabetic retinopathy, nephropathy and neuropathy in Japanese patients with NIDDM. From this study, the glycemic threshold to prevent the onset and the progression of diabetic microangio

Topics: Albuminuria; Blood Glucose; Blood Pressure; C-Peptide; Cholesterol; Cholesterol, HDL; Cohort Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Nephropathies; Diabetic Neuropathies; Diabetic Retinopathy; Female; Humans; Insulin; Japan; Male; Middle Aged; Neural Conduction; Prospective Studies; Statistics, Nonparametric; Time Factors; Triglycerides

To determine whether previously reported abnormalities in fibrinolytic activity and plasma lipoprotein (a) levels could reflect obesity rather than diabetes per se, plasma concentrations of tissue-type plasminogen activator (t-PA), type 1 plasminogen activator inhibitor (PAI-1), and lipoprotein (a) (Lp (a)) were investigated in sixty-four type 2 diabetic patients (56.1 +/- 9.5 years; body mass index, 24.6 +/- 3.3 kg/m2) and thirty-two control subjects (57.9 +/- 8.9 years; body mass index, 24.6 +/- 3.4 kg/m2). Both the plasma t-PA and PAI-1 antigen levels were similar between the diabetic group (10.6 +/- 3.8 ng/ml; 27.7 +/- 11.6 ng/ml) and the control group (12.2 +/- 3.5 ng/ml; 27.7 +/- 9.6 ng/ml). The PAI-1 levels were evenly distributed from 5.93 to 52.7 ng/ml in diabetic patients. The difference of Lp (a) levels between the two groups was negligible (the diabetic group, median 11 mg/dl (range 0-72 mg/dl); the control group, median 13 mg/dl (range 0-55 mg/dl)). Significant correlations between PAI-1 levels and body mass index (BMI) were observed in both groups. In the diabetic group, PAI-1 levels also correlated with fasting C-peptide levels (r = 0.54, P < 0.01) and serum triglyceride levels (r = 0.28, P < 0.05). However, we could not find a significant association between either t-PA or PAI-1 levels and Lp (a) levels in the diabetic and control groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Fibrinolysis; Glycated Hemoglobin; Humans; Hypertension; Korea; Lipids; Lipoprotein(a); Male; Middle Aged; Obesity; Plasminogen Activator Inhibitor 1; Tissue Plasminogen Activator

Altogether 86 patients with recently diagnosed NIDDM, aged 40-64 years were randomised after 3 months of basic education to intensified diet (Int. group, 21 men, 19 women) or conventional treatment groups (Conv. group, 28 men, 18 women). The aim was to examine whether an intensified diet education would result in a better metabolic control and greater reduction in cardiovascular risk factors than conventional treatment for obese patients with recently diagnosed type 2 diabetes mellitus. Furthermore, both groups were re-examined after a second year of observation period to find out the maintenance of the results after intervention. After basic education, Int. group participated in 12-months diet education, while Conv. group was treated in local health centres. During the intervention period, only Int. group showed further weight reduction. Only 20% of patients in Int. and 6% of patients in Conv. group had BMI < 27 kg/m2 at the end of the intervention, while 75% of patients in Int. and 52% of patients in Conv. group had achieved a good metabolic control (fasting blood glucose < 6.7 mmol/l; P = 0.005 between groups). Serum total cholesterol did not change significantly, but the changes in HDL-cholesterol, triglycerides and apolipoprotein B level were significant in Int. group only. The proposed acceptable values for serum lipids were achieved by 52 to 88% of patients without major differences between the two groups. During the second year of observation, weight gained in both groups and a deterioration was seen in metabolic control. Despite that a greater proportion of patients in the Int. group still was in good metabolic control (55.3% vs. 31.8%, P = 0.016), furthermore Int. group was receiving less frequently oral drugs for hyperglycaemia than Conv. group. No differences in serum lipids were observed between the groups after the observation period. HDL-cholesterol showed a persistent improvement in both groups.

Topics: Adult; Apolipoprotein A-I; Apolipoproteins B; Blood Glucose; Blood Pressure; C-Peptide; Cardiovascular Diseases; Cholesterol; Cholesterol, HDL; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diet, Diabetic; Female; Follow-Up Studies; Glucagon; Glycated Hemoglobin; Humans; Male; Middle Aged; Sex Factors; Triglycerides

To investigate the effects of metformin on glycemic control, insulin resistance, and risk factors for cardiovascular disease in NIDDM subjects from two ethnic groups (Caucasian and Asian) with different risks of cardiovascular disease.. A total of 27 subjects with NIDDM (17 Caucasian, 10 Asian) were given metformin and placebo each for a 12-wk period in a randomized, double-blind, placebo-controlled crossover study, and the dose was increased after 1 and 6 wk, up to a maximum of 850 mg three times a day. Insulin resistance, glycemic control, and cardiovascular risk factors were assessed before and after each treatment phase. The end of 12 wk of metformin treatment was compared with the end of 12 wk of placebo treatment.. Metformin treatment was associated with significant improvement in FPG at 6 and 12 wk (mean difference at 12 wk, -3.08 mM, 95% CI -4.12 to -2.04 mM, P < 0.0001) and MCR of glucose (median difference 0.40 ml.kg-1.min-1, interquartile range -0.10 to 1.30 ml.kg-1.min-1, P = 0.036). beta-cell function calculated by HOMA also improved significantly (median difference 14%, interquartile range 7 to 23%, P < 0.001). Total triglyceride (median difference -0.2 mM, interquartile range -0.6 to 0.1 mM, P = 0.034), total cholesterol (mean difference -0.52 mM, 95% CI -0.83 to -0.22 mM, P = 0.002), and LDL cholesterol (mean difference -0.40 mM, 95% CI -0.64 to -0.16 mM, P = 0.002) fell significantly on metformin treatment, whereas no significant changes were observed in HDL cholesterol. PAI-1 activity fell significantly (mean difference -5.3 AU/ml, 95% CI -8.2 to -2.4 AU/ml, P = 0.001), but plasma fibrinogen concentrations and platelet function, spontaneous or agonist induced, were unaffected. UAE was lower on metformin treatment (median difference -2.4 micrograms/min, interquartile range -4.4 to -0.2 micrograms/min, P = 0.004), but metformin had no significant effect on BP. The effects of metformin on glycemic control and cardiovascular risk factors were generally similar in the two ethnic groups.. These findings indicate that metformin treatment improves glycemic control, and lowers insulin resistance and risk factors for cardiovascular disease, including PAI-1, and may therefore be useful in the long-term management of NIDDM subjects who have a high risk of cardiovascular disease.

Topics: Albuminuria; Asia; Biomarkers; Blood Glucose; C-Peptide; Cardiovascular Diseases; Cholesterol; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Double-Blind Method; Ethnicity; Fructosamine; Hexosamines; Humans; Insulin; Insulin Resistance; Islets of Langerhans; Metabolic Clearance Rate; Metformin; Plasminogen Activator Inhibitor 1; Platelet Aggregation; Risk Factors; Triglycerides; United Kingdom; White People

The effect of a blood pressure reduction by 10 mg extended release felodipine once daily on urinary albumin excretion (UAE) as well as the possible diabetogenic effect of felodipine was studied. A 2 X 12 week placebo-controlled double-blind crossover study was performed in 12 hypertensive non-insulin-dependent diabetic (NIDDM) patients without nephropathy on concomitant treatment with beta-blocker and/or a diuretic agent. Metabolic control as estimated by fasting plasma glucose, hemoglobin A1c and fasting plasma C-peptide was unaltered after felodipine. Blood pressure was significantly reduced by felodipine: systolic 166 +/- 26 mm Hg (placebo) v 153 +/- 26 mm Hg (felodipine) (P less than .05) and diastolic 95 +/- 7 mm Hg v 90 +/- 8 mm Hg (P less than .05). Heart rate was unchanged. There was no correlation between blood pressure and UAE, but the relative change in UAE expressed as UAE placebo/UAE felodipine was significantly correlated to the fall in systolic blood pressure (r = 0.64, P = .03) and mean blood pressure (r = 0.66, P = .02). Since microalbuminuria predicts proteinuria and reduced survival, early antihypertensive treatment may be beneficial in NIDDM as it is in IDDM. Long-term consequences on kidney function and mortality remains, however, to be elucidated.

Topics: Aged; Albuminuria; Blood Pressure; C-Peptide; Delayed-Action Preparations; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Double-Blind Method; Fasting; Felodipine; Female; Glycated Hemoglobin; Heart Rate; Humans; Hypertension; Male; Middle Aged

In elderly patients diabetes and hypertension play an important and synergistic role in the development of cardiovascular complications. For this reason therapy must reduce blood pressure without compromising blood glucose control. We investigated the question of whether captopril, an angiotensin converting enzyme inhibitor, can be used without interference to glucose metabolism in diabetics with secondary failure. Ten elderly hypertensive diabetics (diastolic blood pressure greater than 95 mmHg), maintained in good metabolic control using oral hypoglycaemic agents and insulin, were studied before and after 30 days of captopril at 100 mg/day. We measured the following parameters: blood pressure, heart rate, fructosamine and a daily profile for blood glucose and c-peptide. There was a statistically significant reduction in systolic and diastolic blood pressure. No difference was observed in the levels of blood glucose and fructosamine. Insulin secretion as determined by c-peptide levels was not modified, in contrast with findings reported for the use of beta-blockers, diuretics or nifedipine. It seems that captopril is useful and without side effects, even in secondary-failure diabetic patients characterized by unstable metabolic control.

Topics: Aged; Blood Glucose; Blood Pressure; C-Peptide; Captopril; Clinical Trials as Topic; Diabetic Angiopathies; Drug Therapy, Combination; Fructosamine; Hexosamines; Humans; Hypertension; Insulin; Middle Aged

To investigate the association between serum C-peptide level and cardiovascular autonomic neuropathy (CAN) in individuals with type 2 diabetes mellitus (DM) according to estimated glomerular filtration rate (eGFR) METHODS: In a cross-sectional study, we examined 939 individuals with type 2 DM. We measured fasting C-peptide, 2-hour postprandial C-peptide, and ΔC-peptide (postprandial C-peptide minus fasting C-peptide) levels. The individuals were classified into 2 groups based on eGFR: individuals without impaired renal function (eGFR ≥60 ml∙min. Individuals with CAN had lower fasting C-peptide, postprandial C-peptide, and ΔC-peptide levels in patients both with and without impaired renal function. Multivariate logistic regression analyses adjusted for gender, age, and other confounders, including eGFR, showed that serum C-peptide level was significantly associated with CAN (odds ratio [OR] per standard deviation increase in the log-transformed value, 0.67; 95% confidence interval [CI], 0.52-0.87 for fasting C-peptide, P < 0.01; OR, 0.62; 95% CI, 0.47-0.83 for postprandial C-peptide, P < 0.01; OR, 0.71; 95% CI, 0.54-0.93 for ΔC-peptide, P < 0.05).. Serum C-peptide level was negatively associated with CAN in individuals with type 2 DM independent of eGFR.

Topics: Adult; Aged; Autonomic Nervous System; Autonomic Nervous System Diseases; C-Peptide; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Nephropathies; Diabetic Neuropathies; Female; Glomerular Filtration Rate; Humans; Male; Middle Aged; Risk Factors

Fasting serum C-peptide is a biomarker of insulin production and insulin resistance, but its association with vascular complications in type 2 diabetes mellitus (T2DM) has never been fully elucidated. This study aimed to investigate whether C-peptide is associated with cardiovascular disease (CVD) and diabetic retinopathy (DR).. A total of 4793 diabetes patients were enrolled from seven communities in Shanghai, China, in 2018. CVD was defined as a self-reported combination of previous diagnoses, including coronary heart disease, myocardial infarction and stroke. DR was examined using fundus photographs. Logistic regression analyses were performed, and multiple imputed data were used to obtain stabilized estimates.. Prevalence of CVD increased with increasing C-peptide levels (Q1, Q2, Q3 and Q4: 33%, 34%, 37% and 44%, respectively; P. C-peptide was positively associated with CVD, but inversely associated with DR progression. The association between C-peptide and CVD could be due to associated metabolic risk factors.

Topics: Aged; C-Peptide; China; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Humans; Male; Middle Aged; Risk Factors

The aim was to determine if persistent c-peptide in long duration childhood onset (<17 years) type 1 diabetes (T1D) related to microvascular complications.. Pittsburgh Epidemiology of Diabetes Complications (EDC) participants (n = 185) had serum c-peptide levels measured by Mercodia ultra-sensitive ELISA at the 25-year follow-up exam. Microvascular complications between those with and without detectable c-peptide were compared.. Eighteen (9.7%) participants had detectable median c-peptide levels of 3.8 (2.6, 12.2) pmol/L and did not differ from those without detectable levels. No differences in microalbuminuria, confirmed distal symmetric polyneuropathy, renal failure, or between those with one or more complications were found between the two groups. Proliferative retinopathy (PR) was marginally lower in those with detectable c-peptide (33.3% vs 55.1%, p = 0.08). However, those with c-peptide were somewhat less likely to have fasted for a full 8-h (66.7% vs. 84.9%, p = 0.09). Excluding those not fully fasted, PR no longer approached significance but macroalbuminuria became marginally lower in those with detectable levels (23.4% vs 0%, p = 0.07).. Low levels of c-peptide in T1D patients of long duration were detected but were not strongly related to microvascular complications.

Topics: Adolescent; Adult; Albuminuria; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Diabetic Neuropathies; Diabetic Retinopathy; Female; Glycated Hemoglobin; Humans; Male; Risk Factors; Time Factors; Young Adult

Type 2 diabetes is associated with cardiovascular complications. It is largely unknown which patients have poor treatment response and high complication risk; biomarkers are studied for this purpose. The aim of the study was to investigate the association between clinical factors such as HbA1c, level of biomarkers (C-peptide, copeptin) at diagnosis and changes in HbA1c, blood pressure or body mass index (BMI) after five years.. Clinical data and blood samples from 460 newly diagnosed type 2 diabetes patients from the Skaraborg diabetes register (SDR) at diagnosis and after 5years and were analyzed with linear and logistic regressions.. High BMI at diagnosis and smoking were associated with less reduction of HbA1c i.e. poorer treatment outcome after 5years. A high HbA1c at baseline predicted a greater reduction of HbA1c and need for insulin treatment. High systolic blood pressure and BMI at baseline were associated with greater reduction. The biomarkers were not associated with increase of blood pressure, HbA1c, BMI or need for insulin treatment.. Smokers and patients with high HbA1c at diagnosis respond poorer to treatment over 5years. This highlights the importance of advice for non-smoking and weight reduction and more intensive treatment over time.

Topics: Biomarkers; Body Mass Index; C-Peptide; Cardiovascular Diseases; Cohort Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Cardiomyopathies; Female; Follow-Up Studies; Glycated Hemoglobin; Glycopeptides; Humans; Male; Middle Aged; Obesity; Overweight; Prognosis; Registries; Risk Factors; Sweden; Tobacco Smoking

Topics: C-Peptide; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Humans

This study investigated the relationship among β-cell function, metabolic control, and diabetic microvascular complications in patients with type 2 diabetes mellitus (T2DM).. In total, 885 patients with type 2 diabetes mellitus (DM) were recruited from January 2012 to January 2014 and grouped into three groups according to the area under the curve of C-peptide [AUC(C-pep)] during the 75-g oral glucose tolerance test. Logistic regression analyses were used to evaluate the association between C-peptide and microvascular complications.. The prevalence of diabetic microvascular complications decreased from the first to the third AUC(C-pep) tertile (P < 0.01 for all), whereas the rates of nonalcoholic fatty liver disease (NAFLD) was positively associated with AUC(C-pep) values. Patients with lower AUC(C-pep) tertile exhibited higher levels of glycosylated hemoglobin and high-density lipoprotein cholesterol and longer duration of DM; however, levels of triglycerides, fasting C-peptide, 2-h C-peptide, body mass index, and homeostasis model assessment of insulin resistance index were lower compared with the third tertile. Comparison among patients with a similar DM duration showed a higher level of AUC(C-pep) was inversely associated with prevalence of microvascular complications. The odds ratios for nephropathy, retinopathy, and neuropathy in the lowest versus the highest AUC(C-pep) tertile were 3.10 (95% confidence interval, 2.01-4.78), 2.83 (1.73-4.64), and 2.04 (1.37-3.04) after adjustment for confounding factors.. Higher AUC(C-pep) levels were associated with a decreased prevalence of microvascular complications and a good level of glycemic control, whereas higher endogenous insulin levels were linked to the components of metabolic syndrome and increased rates of NAFLD.

Topics: Adult; Aged; Area Under Curve; Blood Glucose; Body Mass Index; C-Peptide; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Fasting; Female; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Insulin Resistance; Insulin-Secreting Cells; Logistic Models; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Odds Ratio; Prevalence; Triglycerides

Topics: Acclimatization; Adaptation, Physiological; Animals; Asthma; Biological Evolution; Blood Vessels; C-Peptide; Calcium; Diabetic Angiopathies; Ecosystem; Hibernation; Humans; Hypoxia; Kidney Tubules; Lung; Receptors, Calcium-Sensing; Respiration

Human C-peptide has a beneficial effect on the prevention of diabetic neuropathy, nephropathy, and vascular complications; however, its role in protection against increased vascular permeability in diabetes remains unclear. Our purpose was to explore the potential protective role of C-peptide against microvascular permeability mediated by vascular endothelial growth factor (VEGF)-induced reactive oxygen species (ROS) generation in diabetes.. Generation of intracellular ROS, real-time changes in intracellular Ca(2+), ROS-dependent stress fibre formation, and the disassembly of the adherens junctions were studied by a confocal microscopy in human umbilical vein endothelial cells (HUVECs). VEGF-induced vascular leakage was investigated in the skin of diabetic mice using a Miles vascular permeability assay. Microvascular leakage in the retina of streptozotocin diabetic mice was investigated using a confocal microscopy after left ventricle injection of fluorescein isothiocyanate (FITC)-dextran. C-peptide inhibited the VEGF-induced ROS generation, stress fibre formation, disassembly of vascular endothelial cadherin, and endothelial permeability in HUVECs. Intradermal injection of C-peptide prevented VEGF-induced vascular leakage. Consistent with this, intravitreal injection of C-peptide prevented the extravasation of FITC-dextran in the retinas of diabetic mice, which was also prevented by anti-VEGF antibody and ROS scavengers in diabetic mice. Conclusions/interpretation C-peptide prevents VEGF-induced microvascular permeability by inhibiting ROS-mediated intracellular events in diabetic mice, suggesting that C-peptide replacement is a promising therapeutic strategy to prevent diabetic retinopathy.

Topics: Adherens Junctions; Animals; C-Peptide; Cadherins; Calcium; Capillary Permeability; Cells, Cultured; Diabetic Angiopathies; Endothelial Cells; Endothelium, Vascular; Human Umbilical Vein Endothelial Cells; Humans; Male; Mice; Mice, Inbred C57BL; Reactive Oxygen Species; Retina; Stress Fibers; Vascular Endothelial Growth Factor A

Vasculopathy is a major complication of diabetes; however, molecular mechanisms mediating the development of vasculopathy and potential strategies for prevention have not been identified. We have previously reported that C-peptide prevents diabetic vasculopathy by inhibiting reactive oxygen species (ROS)-mediated endothelial apoptosis. To gain further insight into ROS-dependent mechanism of diabetic vasculopathy and its prevention, we studied high glucose-induced cytosolic and mitochondrial ROS production and its effect on altered mitochondrial dynamics and apoptosis. For the therapeutic strategy, we investigated the vasoprotective mechanism of C-peptide against hyperglycemia-induced endothelial damage through the AMP-activated protein kinase α (AMPKα) pathway using human umbilical vein endothelial cells and aorta of diabetic mice. High glucose (33 mmol/L) increased intracellular ROS through a mechanism involving interregulation between cytosolic and mitochondrial ROS generation. C-peptide (1 nmol/L) activation of AMPKα inhibited high glucose-induced ROS generation, mitochondrial fission, mitochondrial membrane potential collapse, and endothelial cell apoptosis. Additionally, the AMPK activator 5-aminoimidazole-4-carboxamide 1-β-d-ribofuranoside and the antihyperglycemic drug metformin mimicked protective effects of C-peptide. C-peptide replacement therapy normalized hyperglycemia-induced AMPKα dephosphorylation, ROS generation, and mitochondrial disorganization in aorta of diabetic mice. These findings highlight a novel mechanism by which C-peptide activates AMPKα and protects against hyperglycemia-induced vasculopathy.

Topics: Aminoimidazole Carboxamide; AMP-Activated Protein Kinases; Animals; Apoptosis; C-Peptide; Cells, Cultured; Cytosol; Diabetes Mellitus, Experimental; Diabetic Angiopathies; Enzyme Activation; Glucose; Human Umbilical Vein Endothelial Cells; Humans; Male; Membrane Potential, Mitochondrial; Metformin; Mice; Mice, Inbred C57BL; Mitochondrial Dynamics; Reactive Oxygen Species

This study evaluated the association between serum C-peptide levels and chronic vascular complications in Korean patients with type 2 diabetes. Data for 1,410 patients with type 2 diabetes were evaluated cross-sectionally. Fasting and postprandial 2-hour serum C-peptide levels were analyzed with respect to diabetic micro- and macrovascular complications. In the group of patients with lower fasting serum C-peptide quartile, the prevalences of diabetic retinopathy and neuropathy were significantly higher (P = 0.035, P < 0.001, respectively). In the group of patients with lower delta C-peptide (postprandial - fasting C-peptide) quartile, the prevalences of diabetic retinopathy, nephropathy, and neuropathy were significantly higher (P < 0.001 for all). Low delta C-peptide quartile was also associated with increased severity of retinopathy and nephropathy. The age- and sex-adjusted odds ratios (ORs) for retinopathy, neuropathy, and nephropathy in the lowest versus the highest delta C-peptide quartile were 6.45 (95% confidence interval 3.41-12.22), 3.01 (2.16-4.19), and 2.65 (1.71-4.12), respectively. After further adjustment for the duration of diabetes, type of antidiabetic therapy, mean hemoglobin A1c, body mass index, and blood pressure, the ORs were reduced to 2.83 (1.32-6.08), 1.68 (1.12-2.53), and 1.61 (1.05-2.47), respectively, but remained significant. No significant difference was observed in the prevalence of macrovascular complications with respect to fasting or delta C-peptide quartiles. These results suggest that low C-peptide level is associated with diabetic microvascular, but not macrovascular complications in patients with type 2 diabetes mellitus.

Topics: Adult; Aged; Asian People; C-Peptide; Chronic Disease; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Nephropathies; Diabetic Retinopathy; Female; Humans; Male; Microvessels; Middle Aged; Prevalence; Republic of Korea; Young Adult

Large for gestational age (LAG) neonates who had been exposed to an intrauterine environment of either diabetes or maternal obesity are at increased risk of developing the metabolic syndrome. This can be explained by exposure to high glucose and insulin levels in utero which alter fetal adaptation and programming.. The aim of the study was to evaluate the onset of preclinical atherosclerosis in utero.. We measured umbilical artery wall thickness (ruWT) in the third trimester by obstetric ultrasound and umbilical artery intima-media thickness (uIMT) in pathologic specimens of umbilical cords obtained shortly after delivery and investigated the relation between these measurements and serum insulin level and C-peptide level in cord blood and assessed insulin resistance with the homeostasis model assessment of insulin resistance (HOMA-IR) in infants of diabetic mothers (IDMs), i.e. the study group, which was divided into a large for gestational age group (LGA)-IDM group and an appropriate for gestational age group (AGA)-IDM group and compared with a control group.. The LGA-IDM group had significantly higher insulin (p < 0.001), C-peptide (p = 0.018) and HOMA-IR levels (p < 0.001) compared with the AGA-IDM and control groups. The LGA-IDM group had significantly larger ruWT (p = 0.013) and uIMT (p < 0.001) compared with the AGA-IDM and the control groups. The LGA-IDM group had increased uIMT and ruWT that correlated with the severity of maternal hyperglycemia.. Measurement of ruWT in the third trimester is feasible, reproducible and strongly correlated with pathological serum insulin, C-peptide in cord blood and HOMA-IR levels.

Topics: Adult; Atherosclerosis; C-Peptide; Case-Control Studies; Chi-Square Distribution; Diabetes, Gestational; Diabetic Angiopathies; Female; Fetal Blood; Gestational Age; Glycated Hemoglobin; Humans; Insulin; Insulin Resistance; Predictive Value of Tests; Pregnancy; Pregnancy Trimester, Third; Prospective Studies; Tunica Intima; Tunica Media; Turkey; Ultrasonography; Umbilical Arteries

A protective effect of residual beta-cell function on microvascular complications of type 1 diabetes has been suggested. Our aim was to retrospectively evaluate the association of fasting plasma C-peptide values with micro- and macrovascular complications.. We recruited a clinic-based cohort of 471 type 1 diabetic patients born after 1945 and cared for in the period 1994-2004. Centralized measurements and standardized procedures of ascertainment of micro- and macrovascular complications were employed. Individual cumulative averages of A1C up to 2007 were calculated.. Residual beta-cell secretion was detected even many years after diabetes diagnosis. In multivariate linear regression analysis, fasting plasma C-peptide values were positively associated with age at diagnosis (beta = 0.02; P < 0.0001) and triglycerides (beta = 0.20; P = 0.05) and inversely associated with diabetes duration (beta = -0.03; P < 0.0001) and HDL cholesterol (beta = -0.006; P = 0.03). The final model explained 21% of fasting C-peptide variability. With respect to fasting C-peptide values in the lowest tertile (<0.06 nmol/l), higher values were associated with lower prevalence of microvascular complications (odds ratio [OR] 0.59 [95% CI 0.37-0.94]) independently of age, sex, diabetes duration, individual cumulative A1C average during the study period, hypertension, and cardiovascular diseases. No association was evident with macrovascular complications (0.77 [0.38-1.58]).. Our study shows an independent protective effect of residual beta-cell function on the development of microvascular complications in type 1 diabetes, suggesting the potential beneficial effect of treatment that allows the preservation of even modest beta-cell function over time.

Topics: Adult; Age of Onset; Blood Pressure; Body Mass Index; C-Peptide; Cardiovascular Diseases; Cohort Studies; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Diabetic Nephropathies; Diabetic Neuropathies; Fasting; Female; Humans; Hypertension; Insulin-Secreting Cells; Italy; Male; Multivariate Analysis; Odds Ratio; Regression Analysis

Several intervention studies have convincingly demonstrated the importance of good glycemic control to avoid long-term diabetic complications, but the importance of other risk factors remains controversial. We previously reported a markedly reduced incidence of severe retinopathy and nephropathy during the past decades in an unselected population of type 1 diabetes mellitus diagnosed in childhood. The aim of the present study was to analyze possible risk factors, which could explain the improved prognosis.. In this longitudinal population-based cohort study, we followed all 269 patients in whom type 1 diabetes mellitus was diagnosed in childhood 1961-1985 in a well-defined geographical area in Sweden. The patients were followed until the end of 1990 s. Multivariable regression models were used to analyze the importance of hemoglobin A1c (HbA(1c)), diabetes duration, blood pressure, cardiovascular risk factors and persisting C-peptide secretion for the development of diabetic retinopathy and nephropathy.. Beside longer duration and higher HbA(1c), blood pressure and lipid values were higher and cardiovascular disease and smoking were more common in patients with severe complications. However, multivariable analysis abolished these associations. Diabetes duration and long-term HbA(1c) were the only significant independent risk factors for both retinopathy and nephropathy. The risk of overt nephropathy increased substantially when HbA(1c) was above 9.6% [Diabetes Control and Complications Trial (DCCT) corrected value], while the risk of severe retinopathy increased already when HbA(1c) exceeded 8.6%.. In this unselected population, glycemic control was the only significant risk factor for the development of long-term complications.

Topics: Age of Onset; Albuminuria; Blood Glucose; Blood Pressure; Body Mass Index; C-Peptide; Cardiovascular Diseases; Child; Cholesterol; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Diabetic Nephropathies; Diabetic Retinopathy; Glycated Hemoglobin; Homeostasis; Humans; Triglycerides

We investigated the relation between C-peptide levels and the prevalence of diabetic complications in patients with type 2 diabetes and the metabolic syndrome.. This study includes all patients with diabetes and treated only with oral hypoglycemic agents who were admitted to our department in 2006. The chronic complications of diabetes (vascular disease, retinopathy, nephropathy, neuropathy) were evaluated.. The 77 patients with type 2 diabetes and treated only with oral hypoglycemic agents were divided in two groups, with and without the metabolic syndrome. The two groups did not differ in glycemic control, blood pressure levels, or duration of diabetes. CRP levels were higher in patients with the metabolic syndrome (p=0.03), and nephropathy was more common (70%, compared with 33%). Similar, C-peptide levels were higher in patients with the metabolic syndrome: 3.12+/-1.36 compared with 1.82+/-1.25 (p<0.001). In patients with the metabolic syndrome, C-peptide levels did not differ in patients with or without diabetic complications (3.01+/-1.16, compared with 3.96+/-2.55; p=0.51). Similarly, C-peptide levels in patients without the metabolic syndrome did not differ according to the presence of complications of diabetes (2.25+/-1.21 versus 1.36+/-1.16; p=0.07). However, C-peptide levels were higher in patients with diabetes and the metabolic syndrome who had either nephropathy or vascular disease, compared with those with those complications but without the metabolic syndrome (p=0.01). CRP levels did not correlate with C-peptide levels in any patient group.. Higher C-peptide levels were associated with metabolic syndrome in patients with type 2 diabetes and in diabetes patients who also had nephropathy and vascular disease.

Topics: Aged; Biomarkers; Blood Glucose; C-Peptide; C-Reactive Protein; Confidence Intervals; Diabetes Complications; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Nephropathies; Diabetic Neuropathies; Diabetic Retinopathy; Female; Humans; Hypoglycemic Agents; Male; Metabolic Syndrome; Middle Aged; Prevalence

Low body weight type2 diabetes mellitus (T2DM) is a distinct entity in T2DM having different clinical presentation, morbidity and mortality patterns as well as biochemical profile when compared with classical T2 DM. This study was aimed at comparing three subtypes of T2 DM-overweight (BMI>25), normal weight (BMI>18.5 but <25) and low body weight or lean type2 DM (BM1<18.5). Seventy-five cases of T2 DM (25-lean, 25-normal weight and 25-overweight) were selected. The present study revealed that normal C-peptide level with basal hyperglycaemia is an important characteristic of lean T2 DM. Lower prevalence of hypercholesterolaemia and higher level of triglycerides were found in low body weight T2 DM.Lower prevalence of macrovascular and higher prevalence of microvascular complications are also noted.

Topics: Adult; Blood Glucose; Body Mass Index; Body Weight; C-Peptide; Cholesterol; Comorbidity; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Glycated Hemoglobin; Humans; India; Male; Middle Aged; Triglycerides

Patients with fulminant type 1 diabetes almost completely lack C-peptide even soon after the onset of the disease, and the deficiency continues for the rest of their life. Thus, fulminant type 1 diabetes could serve as a good model of nature to explore the physiological role of C-peptide. For example, patients with fulminant type 1 diabetes have diabetic chronic complications more frequently than those with classical autoimmune type 1 diabetes 5 years after the onset of diabetes, and the higher prevalence could be partly attributable to the complete lack of C-peptide in fulminant type 1 diabetes.

Topics: Biomarkers; C-Peptide; Diabetes Complications; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Humans; Insulin; Insulin Secretion

Recent experimental and clinical data suggest that C-peptide replacement during type 1 diabetes exerts beneficial effects on diabetic nephropathy. The aim of this study was to determine if physiological C-peptide administration in replacement dose during 28 days had beneficial effects on metabolic status and renal functions in type-1 diabetic rats.. Four groups of rats were investigated: a non diabetic group treated with buffer (C group, n=6), three streptozotocin diabetic-induced groups treated with either buffer (D group, n=6), insulin (D-I group, n=6) or rat homologous C-peptide (D-C group, n=6). Weight gain was measured every week. All animals were housed in metabolic cages on day 28 for assessment of metabolic data. Blood and urine samples were collected to allow measurement of plasmatic osmolality, C-peptide concentration, sodium, and glucose losses and proteinuria. Glomerular filtration rate (GFR) was determined by creatinine clearance.. All streptozotocin-treated animals were diabetic. Glycaemic control (mg/dl), was markedly improved in D-I (133+/-65) when compared with either D (547+/-49, P<0.05) or D-C (520+/-48, P<0.05) groups. Conversely, weight gain during the study, was improved in D-I and D-C as compared with D animals (135+/-13 and 41+/-18 vs 18+/-21 respectively), despite different glycaemic control. Diabetes-induced glomerular hyperfiltration (ml/min/kg), urinary protein leakage (g/kg/day), and Na urinary losses (mmol/100 g/day) respectively, were significantly (P<0.05) reduced in D-C (3.95+/-0.6; 0.08+/-0.06; 1.5+/-0.9) in comparison with D (4.95+/-0.8; 0.18+/-0.16; 3.7+/-2.1) and D-I (5+/-0.9; 0.19+/-0.11; 2.7+/-0.8) animals. Plasmatic osmolality was significantly increased in D group whereas there were no differences between C group and D-C group. Food and water intakes, urinary volume as well as urinary glucose losses were not significantly different between D-C and D groups.. C-peptide administration in replacement dose to streptozotocin diabetic rats induces weight gain regardless hyperglycaemia or glycosuria. Diabetic animals supplemented with C-peptide exhibit better renal function resulting in reduced urinary sodium waste and protein excretion together with reduction of the diabetes-induced glomerular hyperfiltration.

Topics: Animals; Blood Glucose; C-Peptide; Diabetes Mellitus, Experimental; Diabetic Angiopathies; Insulin; Kidney; Male; Proteinuria; Rats; Rats, Sprague-Dawley; Sodium; Weight Gain

Increased levels of C-peptide, a cleavage product of proinsulin, circulate in patients with insulin resistance and early type 2 diabetes mellitus. Recent data suggest a potential causal role of C-peptide in atherogenesis by promoting monocyte and T-lymphocyte recruitment into the vessel wall. The present study examined the effect of C-peptide on vascular smooth muscle cells (VSMCs) proliferation and evaluated intracellular signaling pathways involved. In early arteriosclerotic lesions of diabetic subjects, C-peptide colocalized with VSMCs in the media. In vitro, stimulation of human or rat VSMCs with C-peptide induced cell proliferation in a concentration-dependent manner with a maximal 2.6+/-0.8-fold induction at 10 nmol/L human C-peptide (P<0.05 compared with unstimulated cells; n=9) and a 1.8+/-0.2-fold induction at 0.5 nmol/L rat C-peptide (P<0.05 compared with unstimulated cells; n=7), respectively, as shown by [H3]-thymidin incorporation. The proliferative effect of C-peptide on VSMCs was inhibited by Src short interference RNA transfection, PP2, an inhibitor of Src-kinase, LY294002, an inhibitor of PI-3 kinase, and the ERK1/2 inhibitor PD98059. Moreover, C-peptide induced phosphorylation of Src, as well as activation of PI-3 kinase and ERK1/2, suggesting that these signaling molecules are involved in C-peptide-induced VSMC proliferation. Finally, C-peptide induced cyclin D1 expression as well as phosphorylation of Rb in VSMCs. Our results demonstrate that C-peptide induces VSMC proliferation through activation of Src- and PI-3 kinase as well as ERK1/2. These data suggest a novel mechanism how C-peptide may contribute to plaque development and restenosis formation in patients with insulin resistance and early type 2 diabetes mellitus.

Topics: Animals; Arteriosclerosis; C-Peptide; Cell Proliferation; Cells, Cultured; Cyclin D1; Diabetic Angiopathies; Enzyme Activation; Humans; Intracellular Membranes; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Phosphatidylinositol 3-Kinases; Phosphorylation; Phosphotransferases; Proto-Oncogene Proteins c-akt; Rats; Retinoblastoma Protein; Signal Transduction; src-Family Kinases

Topics: Angioplasty, Balloon; Arterial Occlusive Diseases; C-Peptide; Cohort Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Femoral Artery; Humans; Insulin; Recurrence; Ultrasonography

Endogenous and exogenous insulin is suggested to stimulate hypertrophic wound-healing responses and therefore may promote neointimal hyperplasia and restenosis after balloon angioplasty. The ratio of C-peptide to insulin reflects endogenous insulin secretion. In diabetic patients with insulin substitution, lower ratios display a higher proportion of exogenous insulin. The association and interaction of insulin and C-peptide with restenosis after percutaneous transluminal angioplasty (PTA) was investigated in type II diabetic and nondiabetic patients.. The study group included 76 patients (median age, 68 years; interquartile range [IQR], 58-74 years; 55 men [72%]; 31 patients [41%] with type II diabetes) with intermittent claudication (n = 49; 64%) or critical limb ischemia (n = 27; 36%) who underwent primary successful femoral PTA. C-peptide and insulin levels were measured at baseline, and patients were followed to determine restenosis (> or =50%) at 12 months by color-coded duplex sonography.. Restenosis was found in 34 patients (45%) at 12 months. Patients with restenosis had higher insulin levels (median, 21.3 microU/mL IQR, 11.3-35.5 microU/mL) and a lower C-peptide/insulin ratio (median, 16; IQR, 10-21) compared with patients without restenosis (median insulin level, 11.6 microU/mL; IQR, 9.1-22.0 microU/mL [P = .008]; median ratio, 19 [IQR, 17-25], P = .039). In nondiabetic patients, insulin levels were significantly associated with restenosis (P = .046), whereas the ratio of C-peptide to insulin showed no association with restenosis. In patients with type II diabetes (n = 31; 41%), in contrast, the C-peptide/insulin ratio was associated with restenosis (P = .047), whereas insulin levels showed no significant association with restenosis (P = .14).. Insulin levels and the C-peptide/insulin ratio were associated with restenosis after femoral PTA. Exogenous and endogenous insulin may play a role in the pathogenesis of recurrent lumen loss after balloon angioplasty.

Topics: Aged; Angioplasty, Balloon; Arterial Occlusive Diseases; C-Peptide; Cohort Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Femoral Artery; Humans; Insulin; Male; Middle Aged; Recurrence; Ultrasonography

Coronary artery disease (CAD) is the most common cause of death in patients with type 1 diabetes. Asymptomatic CAD is common in uremic diabetic patients, but its prevalence in nonuremic type 1 diabetic patients is unknown. The prevalence of CAD was determined by coronary angiography and the performance of noninvasive cardiac investigation evaluated in type 1 diabetic islet transplant (ITX) candidates with preserved renal function.. A total of 60 consecutive type 1 diabetic ITX candidates (average age 46 years [mean 24-64], 23 men, and 47% ever smokers) underwent coronary angiography, electrocardiographic stress testing (EST), and myocardial perfusion imaging (MPI) in a prospective cohort study. CAD was indicated on angiography by the presence of stenoses >50%. Models to predict CAD were examined by logistic regression.. Most subjects (53 of 60) had no history or symptoms of CAD; 23 (43%) of these asymptomatic subjects had stenoses >50%. CAD was associated with age, duration of diabetes, hypertension, and smoking. Although specific, EST and MPI were not sensitive as predictors of CAD on angiography (specificity 0.97 and 0.93, sensitivity 0.17 and 0.04, respectively) but helped identify two of three subjects requiring revascularization. EST and MPI did not enhance logistic regression models. A clinical algorithm to identify low-risk subjects who may not require angiography was highly sensitive but was applicable only to a minority (n = 8, sensitivity 1.0, specificity 0.27, negative predictive value 1.0).. Nonuremic type 1 diabetic patients with hypoglycemic unawareness and/or metabolic lability referred for ITX are at high risk for asymptomatic CAD despite negative noninvasive investigations. Aggressive management of cardiovascular risk factors and further investigation into optimal cardiac risk stratification in type 1 diabetes are warranted.

Topics: Adult; Aged; Awareness; Blood Pressure; C-Peptide; Coronary Angiography; Coronary Disease; Coronary Stenosis; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Female; Humans; Hypoglycemia; Islets of Langerhans Transplantation; Male; Middle Aged; Postoperative Complications; Predictive Value of Tests; Risk Factors; Sensitivity and Specificity; Smoking

Increased levels of C-peptide, a cleavage product of proinsulin, circulate in patients with insulin resistance and early type 2 diabetes, a high-risk population for the development of a diffuse and extensive pattern of arteriosclerosis. The present study examined the effect of C-peptide on CD4(+) lymphocyte migration, an important process in early atherogenesis. C-peptide stimulated CD4(+) cell chemotaxis in a concentration-dependent manner. This process involves pertussis toxin-sensitive G-proteins as well as activation of phosphoinositide 3-kinase (PI 3-K). Biochemical analysis showed that C-peptide induced recruitment of PI 3-K to the cell membrane as well as PI 3-K activation in human CD4(+) cells. In addition, antidiabetic peroxisome proliferator-activated receptor gamma-activating thiazolidinediones inhibited C-peptide-induced CD4(+) cell chemotaxis as well as PI 3-Kgamma activation. Finally, immunofluorescence staining of thoracic artery specimen of diabetic patients showed intimal CD4(+) cells in areas with C-peptide deposition. Thus, C-peptide might deposit in the arterial intima in diabetic patients during early atherogenesis and subsequently attract CD4(+) cells to migrate into the vessel wall.

Topics: Arteriosclerosis; C-Peptide; CD4-Positive T-Lymphocytes; Cell Movement; Cells, Cultured; Chemotaxis; Diabetic Angiopathies; Enzyme Activation; GTP-Binding Proteins; Humans; Pertussis Toxin; Phosphatidylinositol 3-Kinases; Thiazolidinediones

Latent autoimmune diabetes in adults (LADA) is subtype of diabetes type 1. It is well know, that 50% patients with new diagnosed diabetes type 2 present late complications. As far we don't know how many patients with new diagnosed diabetes have late complications according to presence of antibodies against islet antigens. The aim of the study was to compare late complications of diabetes: microangiopathy and macroangiopathy in newly diagnosed adult diabetic patients in relation to presence of humoral autoimmune markers.. We evaluated the presence of late complications in group of 41, hospitalized patients base on clinical examination and medical history. Glutaminic acid decarboxylase antibodies (anti-GAD), protein tyrosine phosphatase antibodies (anti-IA-2) and anti-insulin antibodies (IAA) titers were measured by RIA. The C peptide basal and stimulated, HbA1c, glucose, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, urea, creatinine levels and microalbuminuria were evaluated.. The presence of islet cell specific antibodies were shown in 25 subjects. We observed late complications in 13/25 (52%) in group with positive antibodies titers, and in 10/16 (62.5%) in group without antibodies. We diagnosed the nephropathy (16% vs 6.25%), retinopathy (12% vs 0%), polyneuropathy (20% vs 12.5%), hypertension (32% vs 50%), chronic heart disease (8% vs 25%), overweight (32% vs 50%) and hyperlipidemia (12% vs 25%) respectively in subjects with and without antibodies. The concentrations of total cholesterol (185 +/- 47.8 vs 218 +/- 38.7, p < 0.05) and creatinine level (0.8 +/- 0.15 vs 0.95 +/- 24, p < 0.05) were higher in group without antibodies, but fasting glycemia (181 +/- 69.1 vs 132 +/- 32.8, p < 0.05) was higher in the group presenting with autoantibodies. We did not observed the difference between level of glycosylated hemoglobin in the investigated groups.. There is the tendency to higher incidence of microangiopathy in group of patients positive to islet cell antibodies. Conversely the macroangiopathy appears frequently in patients without antibodies.

Topics: Adult; Autoantibodies; Biomarkers; C-Peptide; Chronic Disease; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Diabetic Nephropathies; Diabetic Neuropathies; Female; Glutamate Decarboxylase; Humans; Insulin Antibodies; Islets of Langerhans; Male; Middle Aged; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Protein Tyrosine Phosphatases

Our aim was to evaluate the long-term effects of transplanted islets on diabetic macro-/microangiopathy in type 1 diabetic kidney-transplanted patients.. A total of 34 type 1 diabetic kidney-transplanted patients underwent islet transplantation and were divided into two groups: successful islet-kidney transplantation (SI-K; 21 patients, fasting C-peptide serum concentration >0.5 ng/ml for >1 year) and unsuccessful islet-kidney transplantation (UI-K; 13 patients, fasting C-peptide serum concentration <0.5 ng/ml). Patients cumulative survival, cardiovascular death rate, and atherosclerosis progression were compared in the two groups. Skin biopsies, endothelial dependent dilation (EDD), nitric oxide (NO) levels, and atherothrombotic risk factors [von Willebrand factor (vWF) and D-dimer fragment (DDF)] were studied cross-sectionally.. The SI-K group showed a significant better patient survival rate (SI-K 100, 100, and 90% vs. UI-K 84, 74, and 51% at 1, 4, and 7 years, respectively, P = 0.04), lower cardiovascular death rate (SI-K 1/21 vs. UI-K 4/13, chi(2) = 3.9, P = 0.04), and lower intima-media thickness progression than the UI-K group (SI-K group: delta1-3 years -13 +/- 30 micro m vs. UI-K group: delta1-3 years 245 +/- 20 micro m, P = 0.03) with decreased signs of endothelial injuring at skin biopsy. Furthermore, the SI-K group showed a higher EDD than the UI-K group (EDD: SI-K 7.8 +/- 4.5% vs. UI-K 0.5 +/- 2.7%, P = 0.02), higher basal NO (SI-K 42.9 +/- 6.5 vs. UI-K 20.2 +/- 6.8 micro mol/l, P = 0.02), and lower levels of vWF (SI-K 138.6 +/- 15.3 vs. UI-K 180.6 +/- 7.0%, P = 0.02) and DDF (SI-K 0.61 +/- 0.22 vs. UI-K 3.07 +/- 0.68 micro g/ml, P < 0.01). C-peptide-to-creatinine ratio correlated positively with EDD and NO and negatively with vWF and DDF.. Successful islet transplantation improves survival, cardiovascular, and endothelial function in type 1 diabetic kidney-transplanted patients.

Topics: Adult; C-Peptide; Cardiovascular Diseases; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Diabetic Nephropathies; Female; Follow-Up Studies; Humans; Islets of Langerhans Transplantation; Kidney Failure, Chronic; Kidney Transplantation; Male; Survival Rate; Time Factors; Treatment Failure; Treatment Outcome

To assess the occurrence and development of new peripheral arterial occlusive disease (PAOD), its risk factors, and the outcome in patients with type 2 diabetes.. A total of 130 type 2 diabetic patients (mean age 58 years) were examined at baseline and after a mean follow-up of 11 years (range 7-14). The ankle-brachial index (ABI) and toe-brachial index were used to detect PAOD. Blood and urine samples were taken at baseline, and a history of cardiovascular events was recorded during follow-up.. PAOD was diagnosed in 21 (16%) patients at baseline. During follow-up, 21 of 89 (24%) patients developed new PAOD. There were 29 patients who died, 21 (72%) of them from cardiovascular disease. Patients with PAOD suffered an excess mortality compared with patients without PAOD (58 vs. 16%; P < 0.001). Logistic regression analysis showed that PAOD at baseline was associated with age, duration of diabetes, smoking, and urinary albumin excretion rate. Patients who developed new PAOD during follow-up had higher serum LDL cholesterol concentrations and lower HDL cholesterol concentrations and were older than the patients who remained free of PAOD.. Objectively measured PAOD is frequent in type 2 diabetic patients. It presents the early clinical signs of atherosclerosis and is strongly associated with cardiovascular death. The risk factor pattern for PAOD was different at baseline and after a mean follow-up of 11 years. We consider routine ABI measurements and modification of risk factors necessary also in patients with asymptomatic PAOD.

Topics: Age of Onset; Arterial Occlusive Diseases; Brachial Artery; C-Peptide; Cardiovascular Diseases; Cholesterol; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Disease Progression; Electrocardiography; Female; Follow-Up Studies; Humans; Hypertension; Male; Middle Aged; Peripheral Vascular Diseases; Smoking; Survival Rate; Time Factors; Triglycerides

The IGF system is increasingly implicated in the development of cardiovascular disease. The effects of circulating IGFs on the vasculature are largely modulated by IGFBPs, which control their access to cell-surface IGF receptors. IGFBP-1 has been proposed as the acute regulator of IGF bioavailability because of its metabolic regulation by glucoregulatory hormones. Posttranslational phosphorylation of IGFBP-1 significantly increases its affinity for IGF-I and therefore represents a further mechanism for controlling IGF bioavailability. We have therefore examined the IGF system and IGFBP-1 phosphorylation status, using specifically developed immunoassays, in a cohort of 160 extensively characterized type 2 diabetic subjects on two occasions 12 months apart. Total IGFBP-1 (tIGFBP-1), which is predominantly highly phosphorylated, was significantly lower in subjects with known macrovascular disease (geometric mean [95% CI], 48.7 microg/l [33.7-63.6]) than in patients with no vascular pathology (80.0 microg/l [52.2-107]; F = 5.4, P = 0.01). A similar relationship was found for highly phosphorylated IGFBP-1 (hpIGFBP-1) concentration (known macrovascular disease, 45.1 microg/l [35.1-55.2]; no macrovascular disease, 75.8 microg/l [56.2-95.3]; F = 4.8, P = 0.01). Logistic regression showed that for every decrease of 2.73 microg/l in IGFBP-1 concentration, there was a 43% increase in the odds of a subject having macrovascular disease (odds ratio 0.57 [95% CI 0.40-0.83]; P = 0.001). hpIGFBP-1 correlated negatively with systolic blood pressure (rho = -0.30, P < 0.01), diastolic blood pressure (rho = -0.45, P < 0.001), and mean arterial pressure (MAP) (rho = -0.41, P < 0.001). Linear regression modeling showed that 40% of the variance in tIGFBP-1 was accounted for by MAP, triglycerides, and nonesterified fatty acids. In contrast, levels of nonphosphorylated and lesser-phosphorylated IGFBP-1 (lpIGFBP-1) were unrelated to macrovascular disease or hypertension but did correlate positively with fasting glucose concentration (rho = 0.350, P < 0.01). tIGFBP-1 concentrations were higher in subjects treated with insulin alone (n = 29) than for any other group. This effect persisted after adjustment of tIGFBP-1 levels for BMI, C-peptide, age, and sex (F = 6.5, P < 0.001, rho = - 0.46). Such an effect was not apparent for lpIGFBP-1. We conclude that low circulating levels of hpIGFBP-1 are closely correlated with macrovascular disease and hypertension in type 2 diabetes, whereas

Topics: Biomarkers; Blood Glucose; Blood Pressure; C-Peptide; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Ethnicity; Humans; Hypertension; Insulin; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor I; Insulin-Like Growth Factor II; Odds Ratio; Phosphorylation; Predictive Value of Tests; Regression Analysis; Triglycerides

To report the cardiac events in type 2 diabetic outpatients screened for unknown asymptomatic coronary heart disease (CHD) and followed for 5 years.. During 1993, 925 subjects aged 40-65 years underwent an exercise treadmill test (ETT). If it was abnormal, the subjects then underwent an exercise scintigraphy. Of the 925 subjects, 735 were followed for 5 years and cardiac events were recorded.. At the entry of the study, 638 of the 735 followed subjects had normal ETT, 45 had abnormal ETT with normal scintigraphy, and 52 had abnormal ETT and abnormal scintigraphy. The 52 subjects with abnormal scintigraphy and ETT underwent a cardiological and diabetological follow-up; the subjects with just abnormal ETT had a diabetological follow-up only. During the follow-ups, 42 cardiac events occurred: 1 fatal myocardial infarction (MI), 20 nonfatal MIs, and 10 cases of angina in the 638 subjects with normal ETT; 1 fatal MI in the 45 subjects with normal scintigraphy; and 1 fatal MI and 9 cases of angina in the 52 subjects with abnormal scintigraphy. In these 52 subjects all cardiac events were significantly more frequent (chi(2) = 21.40, P < 0.0001) but the ratio of major (cardiac death and MI) to minor (angina) cardiac events was significantly lower (P = 0.002). Scintigraphy abnormality (hazard ratio 5.47; P < 0.001; 95% CI 2.43-12.29), diabetes duration (1.06; P = 0.021; 1.008-1.106), and diabetic retinopathy (2.371; P = 0.036; 1.059-5.307) were independent predictors of cardiac events on multivariate analysis.. The low ratio of major to minor cardiac events in the positive scintigraphy group may suggest, although it does not prove, that the screening program followed by appropriate management was effective for the reduction of risk of major cardiac events.

Topics: Age Distribution; Aged; Blood Pressure; Body Mass Index; C-Peptide; Coronary Disease; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Exercise Test; Follow-Up Studies; Humans; Italy; Lipids; Mass Screening; Middle Aged; Proportional Hazards Models; Smoking

Several studies have demonstrated an association of CTLA4 (IDDM12) alanine-17 with type 1 diabetes, but CTLA4 variants have not yet been investigated in type 2 diabetes. The CTLA4 exon 1 polymorphism (49 A/G) was analyzed in 300 Caucasian patients with type 2 diabetes and 466 healthy controls. All patients were negative for glutamate decarboxylase and islet cell antibodies. CTLA4 alleles were defined by PCR, single-strand conformational polymorphism, and restriction length fragment polymorphism analysis using BBV:I. The distribution of alleles as well as the genotypic and phenotypic frequencies were similar among patients and controls [AA, 42 vs. 39%; AG, 47 vs. 46%; GG, 11 vs. 15%, P = not significant (n.s.); A/G, 65/35% vs. 62/38%, P = n.s.; alanine/threonine 92/58% vs. 85/61%, P = n.s.]. However, detailed analysis of clinical and biochemical parameters revealed a tendency of GG (alanine/alanine) toward younger age at disease manifestation (46.8 +/- 0.8 vs. 49.5 +/- 0.8 yr, mean +/- SEM), lower body mass index (21.4 +/- 0.5 vs. 24.4 +/- 0.5 kg/m(2), P = 0.042), and basal C-peptide level (0.33 +/- 0.07 vs. 0.53 +/- 0.07nmol/L), as well as earlier start of insulin treatment (5.8 +/- 1.2 vs. 8.7 +/- 0.6 yr) and higher portion of patients on insulin (71 vs. 61%). Patients with the AA genotype were significantly less likely to develop microangiopathic lesions (P < 0.0005). No differences were found for hypertension or family history of type 2 diabetes. In conclusion, CTLA4 alanine-17 does not represent a major risk factor for type 2 diabetes. Additional studies on larger groups and different ethnic groups are warranted to clarify the association of the GG genotype with faster ss-cell failure and the lower rate of microvascular complications in AA carriers.

Topics: Abatacept; Amino Acid Substitution; Antigens, CD; Antigens, Differentiation; C-Peptide; Codon; CTLA-4 Antigen; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Nephropathies; Diabetic Neuropathies; Diabetic Retinopathy; Female; Germany; HLA-DQ alpha-Chains; HLA-DQ Antigens; HLA-DQ beta-Chains; Humans; Immunoconjugates; Immunoglobulin Fc Fragments; Male; Middle Aged; Phenotype; Polymorphism, Genetic; Reference Values; White People

Insulin resistance is known as an important risk factor for coronary artery disease (CAD). However, CAD-related mortality in Japanese type 2 diabetics is lower than in Caucasians. To investigate whether insulin resistance is related to CAD in Japanese type 2 diabetics, we measured insulin sensitivity and several coronary risk factors in Japanese patients with type 2 diabetes with and without CAD. Thirty-three patients with definite CAD and 33 age- and sex-matched patients without CAD (control) were studied. Insulin sensitivity was assessed by the K index of insulin tolerance test (KITT). Clinical characteristics, classical risk factors, lipoprotein (a), and insulin sensitivity were compared between the two groups. Patients with CAD had a significantly longer duration of diabetes (9.0 +/- 1.4 vs. 5.5 +/- 0.9 years, P < 0.05, respectively), were mostly hypertensive (69.7 vs. 39.4%, P < 0.05), and more likely to be treated with insulin (45.5 vs. 18.2%, P < 0.05) compared with the control. Concerning the metabolic parameters, patients with CAD had a significantly higher insulin resistance than control (2.40 +/- 0.15 vs. 3.23 +/- 0.17%/min, P < 0.01, respectively), higher triglyceride (1.39 +/- 0.10 vs. 1.05 +/- 0.05 mmol/l, P < 0.05), lower HDL cholesterol (1.05 +/- 0.05 vs. 1.28 +/- 0.06 mmol/l, P < 0.05), and higher lipoprotein (a) (27.5 +/- 4.3 vs. 17.4 +/- 2.0 mg/dl, P < 0.05). Multiple logistic regression analysis indicated that hypertension, insulin resistance, high lipoprotein (a) and triglyceride, and low HDL cholesterol were independently related to CAD. Our results suggest that insulin resistance per se is a significant risk factor for CAD in Japanese patients with type 2 diabetes.

Topics: Aged; Asian People; Blood Glucose; Blood Pressure; C-Peptide; Cholesterol; Cholesterol, HDL; Coronary Disease; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Glycated Hemoglobin; Humans; Insulin Resistance; Japan; Lipoprotein(a); Male; Middle Aged; Myocardial Infarction; Risk Factors; Smoking; Triglycerides; White People

The influence of the hormones most involved in glucose homeostasis, C-peptide, insulin and glucagon on blood viscosity was tested in vitro. Whole blood (adjusted to haematocrit 45%) from healthy volunteers (n=24) and patients with diabetes mellitus (n=17) was incubated with 10(-7)-10(-10) M C-peptide, insulin or glucagon. None of these peptide hormones, neither at physiological nor at supraphysiological levels, had an influence on high (94.5 s(-1)) or low (0.1 s(-1)) shear rate viscosity. The small group of diabetic patients had a higher plasma viscosity and increased blood viscosity at 94.5 s(-1), which is in agreement with earlier studies, but decreased viscosity at low shear rate. We conclude that C-peptide, insulin and glucagon have no direct effect on blood viscosity in vitro. It is, therefore, unlikely that microvascular disturbances seen with either deficiency or excess of these hormones is due to haemorheological factors.

Topics: Adult; Aged; Blood Proteins; Blood Viscosity; C-Peptide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Dose-Response Relationship, Drug; Erythrocyte Indices; Female; Glucagon; Glycated Hemoglobin; Humans; Insulin; Male; Middle Aged

To analyse the clinical characteristics and relevant hormonal profile in type 1 diabetic patients with and without ED.. Fifty one type 1 diabetic patients were studied. ED was assessed by direct interview. Chronic diabetic complications, smoking and alcohol status as well as current use of medications were recorded. Hormonal profile consisted of plasma LH, FSH, prolactin, androstenedione (Delta(4)), dehydroepiandrosterone (DHEA), DHEA-sulfate (DHEA-S), free testosterone (FT), estradiol (E(2)), sex hormone binding globulin (SHBG), dihydrotestosterone (DHT), cortisol, TSH and free thyroxine (FT(4)).. ED was present in 24 patients (47%) (group 1), who were older (P<0.001), had a longer diabetes duration (P<0.001) and a higher systolic blood pressure (P=0.017) when compared to the subjects who did not complain (group 2). ED was positively correlated to all diabetes-related complications (P<0.02). Antidepressive drug(s) were more frequent in group 1 (P=0.007), as well as prokinetics (P=0.043) and ACE-inhibitors (P=0.010). HbA(1)c was comparable. Patients with ED had lower levels of Delta(4) (P=0.003), DHEA (P<0.001), DHEA-S (P=0.002), FT (P=0.08) while SHBG (P=0.010) and LH (P=0.022) were higher compared to group 2. Multiple logistic regression analysis showed an independent association of ED with Delta(4) (P=0.016), DHEA-S (P=0.037), SHBG (P=0.001) and insulin dose (P=0.025). There was no significant difference for all other measured hormones.. ED is impressively prevalent in type 1 diabetes and is associated with age, diabetes duration, chronic complications and decreased androgens.

Topics: Age Factors; Alcohol Drinking; Androgens; Blood Pressure; C-Peptide; Cohort Studies; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Diabetic Neuropathies; Diabetic Retinopathy; Erectile Dysfunction; Estradiol; Follicle Stimulating Hormone; Humans; Hydrocortisone; Hypertension; Luteinizing Hormone; Male; Middle Aged; Prolactin; Smoking

Syndrome X is used to describe a constellation of factors that lead to coronary heart disease (CHD): hypertension, hyperinsulinemia, impaired glucose tolerance, and an abnormality in lipid metabolism. We investigated the relationship between serum levels of C-peptide immunoreactivity (CPR) and diabetic complications in 256 patients with type-2 diabetes mellitus. The serum level of CPR was measured by radioimmunoassay (RIA). Diabetic patients were divided into 3 groups according to the serum level of CPR as follows: low CPR (n = 19, <0.7 ng/ml), normal CPR (n = 174, 0.7 to 2.2 ng/ml) and high CPR (n = 63, >2.2 ng/ml). The body mass index (BMI) and the serum level of triglycerides were significantly higher in the high CPR group (P < 0.05, respectively) compared with normal CPR group. The prevalence of hypertension was significantly higher in the high CPR group than in the other 2 groups (low CPR: 16%, normal CPR: 28%, high CPR: 38%). The frequency of the number of patients receiving insulin therapy was greater in the low CPR group than in the other 2 groups, (low CPR: 58%, normal CPR: 15%, high CPR: 11%). The serum CPR level was significantly lower in patients with than without proliferative retinopathy or macroalbuminuria. Our conclusion is that the present data suggest that an increased serum level of CPR is associated with obesity, elevated serum triglycerides, and hypertension in patients with type-2 diabetes mellitus. A low CPR level leading to hyperglycemia is associated with the progression of diabetic microangiopathies, such as retinopathy and nephropathy.

Topics: Albuminuria; Body Mass Index; C-Peptide; Coronary Disease; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Retinopathy; Female; Humans; Hypertension; Hypertriglyceridemia; Insulin; Male; Middle Aged; Obesity; Risk Factors

A sub-study evaluated 698 younger (54.5 +/- 6.9 years) type 2 diabetics of the KID Study participants to establish the prevalence of diabetic complications and associated diseases and their correlation with body mass index (BMI), duration of disease and to C-peptide levels. Only 19.8% of the type 2 diabetics had a normal weight. In all weight subgroups, the average age of diabetes manifestation were around age 45. In 46.6% of all type 2 diabetics we could already demonstrate microangiopathic complications. Strikingly, 15.9% of the patients already had proliferative retinopathies and 12.6% had albuminuria of more than 1000 mg/dl. 74.7% of our type 2 diabetics presented with the well-known risk cluster of the metabolic syndrome: In every other patient, we found hypertension and/or hyperlipoproteinaemia. Accordingly, the prevalence of the macroangiopathic diabetic complications, coronary artery disease and peripheral vascular disease was 17.8%, which is high for a relatively young population with a mean age of 53.9 years and goes conform with recent literature (Lowel et al., 1999). An increase in BMI correlated significantly with deterioration of HbA1, a decrease in HDL cholesterol, an increase in triglycerides and with a higher prevalence of hypertension. The frequency of nephropathy increase significantly up to a BMI of 30-35 kg/m2. Retinopathies and polyneuropathies were associated with BMI but increased significantly with the duration of the diabetic state. In contrast to microangiopathic diabetic complications, there was already a high prevalence of nephropathy after a comparatively short duration of disease. The prevalence of hyperlipoproteinaemia and hypertension did not depend from the duration of diabetes. These concomitant diseases already were frequent early in the disease and did not increase with the duration of disease. However, there was a strong correlation between increasing hyperlipoproteinaemia and hypertension and higher C-peptide levels. We found no coincidence between C-peptide levels and microangiopathic diabetic complications.

Topics: Adult; Body Mass Index; C-Peptide; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Nephropathies; Diabetic Neuropathies; Diabetic Retinopathy; Female; Germany; Humans; Male; Middle Aged; Prevalence; Prospective Studies; Randomized Controlled Trials as Topic; Time Factors

The aim of this study was to determine whether renal functional reserve (RFR) is altered in insulin-dependent diabetic (IDDM) patients according to the stage of diabetic nephropathy. RFR was examined in 33 IDDM patients in similar glycaemic and metabolic control and compared to 12 healthy control subjects, during eight 1 h clearance periods prior to, during and after a 3-h stimulation by amino acid infusion (4.5 mg x kg(-1) x min[-1]). RFR was calculated as the difference between stimulated and baseline glomerular filtration rates (GFR). In 14 early normotensive diabetic patients with normal urinary albumin excretion, mean baseline GFR (133 +/- 3 ml x min(-1) x 1.73 m[-2]) was higher whereas RFR (10 +/- 4 ml x min(-1) x 1.73 m[-2]) was lower (p < 0.05) than in control subjects (113 +/- 4 and 28 +/- 2 ml x min(-1) x 1.73 m(-2), respectively). In 10 normotensive patients who had lived with IDDM for 16 years and who had microalbuminuria, baseline GFR and RFR (109 +/- 7 and 24 +/- 6 ml x min(-1) x 1.73 m(-2), respectively) were similar to those in control subjects. In 9 patients who had suffered IDDM for 23 years and had developed macroalbuminuria and hypertension, baseline GFR (78 +/- 8 ml x min(-1) x 1.73 m[-2]) was lower than in control subjects (p < 0.05) and RFR (8 +/- 4 ml x min(-1) x 1.73 m[-2]) was not significant. In addition, renal vascular resistance decreased significantly during infusion (p < 0.05) in microalbuminuric normotensive patients as well as in control subjects (by 9 +/- 4 and 11 +/- 4 mmHg x l(-1) x min(-1) x 1.73 m(-2), respectively) but not in normoalbuminuric normotensive or macroalbuminuric hypertensive patients. These results indicate that microalbuminuric normotensive patients retain a normal RFR, whereas RFR is reduced or suppressed at two opposite stages of the disease: in normoalbuminuric normotensive patients with a high GFR and in macroalbuminuric hypertensive patients with a decreased GFR. This dissimilar impairment reveals permanent glomerular hyperfiltration in both early IDDM without nephropathy and IDDM with overt diabetic nephropathy, but not in IDDM with incipient nephropathy.

Topics: Adult; Albuminuria; Aldosterone; Amino Acids; Blood Glucose; Blood Pressure; C-Peptide; Creatinine; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Diabetic Nephropathies; Dietary Proteins; Female; Glomerular Filtration Rate; Glycated Hemoglobin; Humans; Hypertension; Kidney; Male; Reference Values; Renal Circulation; Renin; Vascular Resistance

To identify the clinical characteristics of early-onset NIDDM patients with severe diabetic complications.. The clinical cases of a large number of diabetic patients who visited a diabetes center within the period 1970-1990 were reviewed. Of a total of 16,842 diabetic patients, 1,065 (6.3%) had early-onset NIDDM (diabetes diagnosed before 30 years of age). These 1,065 patients were divided into two groups, those who developed proliferative retinopathy before the age of 35 (n = 135) and those who did not (n = 930). Development of proliferative retinopathy, nephropathy, renal failure, blindness, and atherosclerotic vascular disease were compared between the two groups.. The subgroup of 135 patients was characterized by poor glycemic control, often requiring insulin therapy and a higher familial prevalence of diabetes, and contained a greater proportion of women than the subgroup of 930 patients. Of the 135 patients, 99 (67%) developed proliferative retinopathy before the first visit. The 135 patients developed severe progressive complications in contrast to the 930 patients. A total of 81 patients (60%) developed diabetic nephropathy at a mean age of 31 years, 31 (23%) developed renal failure requiring dialysis at a mean age of 35 years, 32 (24%) became blind at a mean age of 32 years, and 14 (10%) developed atherosclerotic vascular disease at a mean age of 36 years.. Some Japanese early-onset NIDDM patients develop severe diabetic complications in their youth. Most of them had no symptoms nor regular treatment regarding diabetes until they were noticed to have developed severe diabetic complications. Although the relevant prevalence and the pathogenetic mechanism underlying the rapid onset of the complications remain to be determined, prolonged inadequate treatment of and familial predisposition to diabetes may be contributing factors. Careful diabetes care in the twenties, not only for IDDM but also for NIDDM patients, is warranted.

Topics: Adult; Age Factors; Age of Onset; Arteriosclerosis; Blindness; Body Mass Index; C-Peptide; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Nephropathies; Diabetic Retinopathy; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Japan; Kidney Failure, Chronic; Male; Middle Aged; Retrospective Studies

C-peptide, a cleavage product from the processing of proinsulin to insulin, has been considered to possess little if any biological activity other than its participation in insulin synthesis. Injection of human C-peptide prevented or attenuated vascular and neural (electrophysiological) dysfunction and impaired Na+- and K+-dependent adenosine triphosphate activity in tissues of diabetic rats. Nonpolar amino acids in the midportion of the peptide were required for these biological effects. Synthetic reverse sequence (retro) and all-D-amino acid (enantio) C-peptides were equipotent to native C-peptide, which indicates that the effects of C-peptide on diabetic vascular and neural dysfunction were mediated by nonchiral interactions instead of stereospecific receptors or binding sites.

Topics: Amino Acid Sequence; Animals; Blood Circulation; Blood Glucose; C-Peptide; Capillary Permeability; Circular Dichroism; Diabetes Mellitus, Experimental; Diabetic Angiopathies; Diabetic Neuropathies; Humans; Male; Molecular Sequence Data; Neural Conduction; Peptide Fragments; Protein Structure, Secondary; Rats; Rats, Sprague-Dawley; Sodium-Potassium-Exchanging ATPase; Stereoisomerism

Topics: C-Peptide; Diabetic Angiopathies; Diabetic Nephropathies

The majority (> 80%) of patients with non insulin dependent diabetes mellitus (NIDDM) present in Europe and America are obese. In developing countries like India, most NIDDM (> 60%) are non-obese and many are actually lean with a body mass index (BMI) of < 18.5 and are referred to as 'lean NIDDM'. This paper compares the clinical profile of a cohort of 347 lean NIDDM, with a group of 6274 NIDDM of ideal body weight (IBW) and 3252 obese NIDDM attending a diabetes centre at Madras in South India. The lean NIDDM who constituted 3.5% of all NIDDM patients seen at our centre, had more severe diabetes and an increased prevalence of retinopathy (both background and proliferative), nephropathy and neuropathy. Although a larger percentage of the lean NIDDM patients were treated with insulin, 47% of the males and 53% of the females were still on oral hypoglycaemic agents even after a mean duration of diabetes of 9.2 +/- 8.1 years. Studies of GAD antibodies, islet cell antibodies (ICA) and fasting and stimulated C-peptide estimations done in a small subgroup of the lean NIDDM showed that they were distinct from IDDM patients. More studies are needed on metabolic, hormonal and immunological profile of lean NIDDM seen in developing countries like India.

Topics: Adult; Autoantibodies; Blood Glucose; Blood Pressure; Body Mass Index; Body Weight; C-Peptide; Cholesterol; Cohort Studies; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Neuropathies; Diabetic Retinopathy; Diastole; Dose-Response Relationship, Drug; Fasting; Female; Glutamate Decarboxylase; Glycated Hemoglobin; Humans; Hypoglycemic Agents; India; Insulin; Islets of Langerhans; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Obesity; Postprandial Period; Smoking; Systole; Triglycerides

Macrovasular disease is the most important cause of morbidity and mortality in Type 2 (non-insulin-dependent) diabetes. Dyslipidaemia and hyperinsulinaemia have been proposed as aetiological factors. This paper describes the interrelationships between fasting serum insulin, serum lipids, and the extent of ultrasonically measured early arterial disease in Type 2 diabetic subjects screened for entry into a prospective study set up to ascertain whether improving serum lipids can alter the progress of arterial disease in Type 2 diabetes. Measurements were made of the initima media thickness (IMT) in the carotid artery, and an arterial ultrasound score (AUS) based on appearances of both carotid and femoral arteries was calculated for 192 established Type 2 diabetic subjects, males and females, mean age 51 (range 35-66) years, median duration of diabetes 3.5 years, with no known cardiovascular disease. Multiple regression analysis showed that carotid IMT increased with age and was inversely related to serum insulin (variance accounted for, R2, = 8.8%, p = 0.0002). AUS increased with age and was related inversely to serum insulin, or to C-peptide when this was substituted in the model. In addition to age and serum insulin, AUS was positively associated with non-HDL cholesterol and negatively with HDL 3 cholesterol (R2 = 26%, p = 0.0001). Early thickening and damage to the arterial wall in Type 2 diabetes may be related to relative fasting hypoinsulinaemia.

Topics: Adult; Aged; Arterial Occlusive Diseases; Blood Glucose; C-Peptide; Carotid Arteries; Carotid Artery Diseases; Cholesterol; Cholesterol, HDL; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Fasting; Female; Femoral Artery; Glycated Hemoglobin; Humans; Insulin; Lipids; Male; Middle Aged; Regression Analysis; Tunica Media; Ultrasonography

To evaluate the relationship between islet cell antibodies (ICAs) and the cardiovascular risk profile 5 years after clinical diagnosis of NIDDM.. Five years after clinical diagnosis, we evaluated blood pressure (BP) and lipids in 17 NIDDM patients with ICA at diagnosis (age 60 +/- 4 years) and 133 NIDDM patients without ICA at diagnosis (age 61 +/- 1 year). Urinary albumin excretion was evaluated in a subset of 12 NIDDM patients with ICA at diagnosis (age 60 +/- 4 years) and 82 NIDDM patients without ICA at diagnosis (age 61 +/- 1 year).. NIDDM patients without ICA showed higher BP (140/86 +/- 2/1 mmHg vs. 128/79 +/- 3/2 mmHg; P < 0.05), total cholesterol (6.10 +/- 0.11 vs. 5.09 +/- 0.29 mmol/l; P < 0.01), LDL-to-HDL ratio (3.85 +/- 0.14 vs. 2.49 +/- 0.18; P < 0.001), and triglycerides (2.58 +/- 0.24 vs. 0.90 +/- 0.06 mmol/l; P < 0.001), lower HDL cholesterol (1.08 +/- 0.03 vs. 1.40 +/- 0.08 mmol/l; P < 0.001), and higher urinary albumin excretion (0.16 +/- 0.06 vs. 0.01 +/- 0.01 g/24 h; P < 0.05) than NIDDM patients with ICA. Among NIDDM patients without ICA, no differences concerning BP or lipids were found between obese and nonobese patients.. ICA at diagnosis of NIDDM is a marker of more favorable cardiovascular risk profile 5 years after clinical diagnosis.

Topics: Adult; Autoantibodies; Biomarkers; Blood Glucose; Blood Pressure; C-Peptide; Cardiovascular Diseases; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Follow-Up Studies; Humans; Hypertension; Islets of Langerhans; Middle Aged; Predictive Value of Tests; Risk Factors; Time Factors; Triglycerides

Sex hormones are associated with atherogenic changes in lipoproteins and changes in glucose and insulin metabolism, yet few data are available on the relationship of sex hormones and dehydroepiandrosterone sulfate (DHEA-SO4) to ischemic heart disease (IHD) in diabetic subjects, a group with very high levels of IHD.. We examined the relation of total and free testosterone, sex hormone binding globulin, estrone, estradiol, and DHEA-SO4 to the 5-year IHD mortality in the older-onset diabetic subjects in the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) in a matched diabetic subject-control design (two control subjects for every diabetic subject).. In men (n = 123), none of the sex hormones or DHEA-SO4 significantly predicted IHD mortality. In women (n = 120), lower levels of DHEA-SO4 (P < 0.01) and total testosterone (P = 0.07) predicted IHD mortality. These results were essentially unchanged after adjustment for duration of diabetes, GHb, diuretic use, and serum creatinine, which are major predictors of IHD mortality in the WESDR. Finding lower testosterone levels in diabetic subjects of IHD in women is contrary to data on risk factors, which suggests that increased androgen activity may be associated with worse IHD risk factors.. This study suggests that alterations in sex hormones and DHEA-SO4 are unlikely to explain a major proportion of the variation in IHD mortality in diabetic subjects.

Topics: Adult; Age of Onset; Aged; Biomarkers; C-Peptide; Cross-Sectional Studies; Dehydroepiandrosterone Sulfate; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Retinopathy; Estradiol; Estrone; Female; Humans; Hypertension; Male; Middle Aged; Myocardial Ischemia; Predictive Value of Tests; Proteinuria; Sex Characteristics; Sex Hormone-Binding Globulin; Smoking; Testosterone; Wisconsin

Topics: Adolescent; Antioxidants; Ascorbic Acid; Biomarkers; C-Peptide; Child; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Erythrocytes; Humans; Insulin; Insulin Secretion; Vitamin E

Variations in serum Lp(a) concentrations were studied in a large population of non-insulin-dependent diabetic (NIDDM) patients in relation to long-term complications. Lp(a) concentrations were measured by immunonephelometry in 819 NIDDM subjects and compared with those of 128 controls. Correlations were investigated relative to plasma lipid and glycaemic parameters, body mass index (BMI) and macro- and microvascular complications. Mean absolute and relative variations of Lp(a) concentrations were studied in a subgroup of 245 patients over a one-year period. No significant differences were found between Lp(a) concentrations in NIDDM and control subjects. No relationship was evidenced with macrovascular and microvascular complications or glycaemic control. Mean relative Lp(a) variations were correlated with BMI and absolute and relative variations in triglyceridaemia. These results confirm the absence of any alterations of Lp(a) concentrations in a large cohort of NIDDM patients, either with or without micro- and macrovascular complications, but suggest a particular modulatory role for BMI and serum triglyceride variations.

Topics: Adult; Apolipoproteins B; Blood Glucose; Body Mass Index; C-Peptide; Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Fasting; Female; Humans; Lipoprotein(a); Male; Middle Aged; Postprandial Period; Reference Values; Triglycerides

Topics: Blood Glucose; C-Peptide; Cell Adhesion Molecules; Diabetes Mellitus, Type 2; Diabetic Angiopathies; E-Selectin; Female; Glycated Hemoglobin; Humans; Insulin; Intercellular Adhesion Molecule-1; Male; Middle Aged; Reference Values; Vascular Cell Adhesion Molecule-1

To compare platelet plasminogen activator inhibitor 1 (PAI-1) release in type II diabetic patients and healthy control subjects.. We studied a group of 27 diabetic patients and a group of 16 nondiabetic control subjects. Whole-blood platelet aggregation, defined as a decrease in platelet count during shaking (180 rpm) of blood samples at 37 degrees C, and plasma PAI-1 antigen concentrations were measured in parallel at time 0, 7.5, 15, 30, 60, 120, and 180 min.. Platelet aggregation did not differ significantly between the two groups at any time period. However, the increase in plasma PAI-1 antigen concentration over basal levels at time 0 was higher for the group of diabetic patients when compared with their matched control subjects. The increment of PAI-1 antigen was 61.8 +/- 29.4 vs. 35.9 +/- 13.4 ng/ml (P < 0.005, means +/- SD) after 180 min for the diabetic and control subjects, respectively. Platelet PAI-1 release was correlated to very-low-density lipoprotein cholesterol and triglyceride plasma levels, but not to HbA1c levels.. Platelets of patients with type II diabetes release significantly more PAI-1 than platelets of healthy subjects at the same level of platelet aggregation. This may contribute to enhanced thrombosis in diabetes.

Topics: Adult; Aged; Analysis of Variance; Blood Platelets; C-Peptide; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Cholesterol, VLDL; Cohort Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Glycated Hemoglobin; Humans; Hypertension; In Vitro Techniques; Insulin; Male; Middle Aged; Plasminogen Activator Inhibitor 1; Platelet Activation; Platelet Aggregation; Reference Values; Triglycerides

We have examined the impact of hypertension and blood glucose control on insulin sensitivity in obese Type 2 (non-insulin-dependent) diabetic patients. Glucose metabolism in the basal state and in response to insulin was examined using the euglycaemic, hyperinsulinaemic (2 mU kg-1 min-1) clamp technique in combination with 3-[3H]-glucose infusion and indirect calorimetry in 60 obese Type 2 diabetic patients (30 normotensive patients and 30 hypertensive patients on antihypertensive treatment) and 10 obese normotensive control subjects. In the basal state and during hyperinsulinaemia, glucose disposal rates (total, oxidative, and nonoxidative) were similar in Type 2 diabetic patients with or without hypertension (230 +/- 83 vs 270 +/- 114 mg m-2 min-1 (NS), 83 +/- 28 vs 95 +/- 7 mg m-2 min-1 (NS), 148 +/- 70 vs 180 +/- 89 mg m-2 min-1 (NS), treated hypertensive vs normotensive subjects, respectively). However, compared to obese control subjects (403 +/- 65 mg m-2 min-1) both groups of diabetic patients had significantly decreased insulin-stimulated glucose disposal rates (p < 0.005). Even in a subset of Type 2 diabetic patients with long-term (> 6 months) near normal blood glucose control (HbA1c < 6.1%) significant defects were detectable in whole-body glucose and lipid metabolism when compared to control subjects. These results indicate that treated hypertension does not significantly aggravate the insulin insensitivity that is already present in Type 2 diabetes mellitus. Furthermore, Type 2 diabetic patients with long-term good metabolic control continue to demonstrate insulin insensitivity in peripheral tissues.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Calorimetry; Case-Control Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Fatty Acids, Nonesterified; Female; Glucose; Glucose Clamp Technique; Humans; Insulin; Lipid Metabolism; Liver; Male; Middle Aged; Obesity; Oxidation-Reduction; Patient Compliance; Reference Values

Topics: Age Factors; Aged; Analysis of Variance; Blood Pressure; Body Mass Index; C-Peptide; Cardiovascular Diseases; Creatinine; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Follow-Up Studies; Glucagon; Humans; Insulin; Insulin Secretion; Male; Morbidity; Myocardial Ischemia; Obesity; Risk Factors; Sex Factors

Both vascular disease and elevated concentrations in plasma of plasminogen activator inhibitor type-1 (PAI-1) are prominent in patients with non-insulin-dependent diabetes mellitus (NIDDM). We and others have hypothesized that the increased PAI-1 may contribute to acceleration of atherosclerosis in this condition and in other states characterized by insulin resistance as well. Surprisingly, however, elevations of PAI-1 decrease when type II diabetic patients are treated with exogenous insulin, as do circulating concentrations of the precursor of insulin, proinsulin, in plasma. Accordingly, the increased PAI-1 in patients with NIDDM may reflect effects of precursors of insulin rather than or in addition to those of insulin itself. To assess this possibility directly, this study was performed to identify potential direct effects of proinsulin and proinsulin split products on synthesis of PAI-1 in liver cells, thought to be the major source of circulating PAI-1 in vivo.. Hep G2 cells (highly differentiated human hepatoma cells) were exposed to human proinsulin, des(31,32)proinsulin and des(64,65)proinsulin (split products of proinsulin), or C-peptide. Accumulation of PAI-1 in conditioned media increased in a time- and concentration-dependent fashion in response to the two des-intermediates [3.3-fold with des(31,32)proinsulin and 4.5-fold with des(64,65)proinsulin]. C-peptide elicited no increase. Stimulation was transduced at least in part by the insulin receptor as shown by inhibition of stimulation by insulin receptor antibodies, mediated at the level of PAI-1 gene expression as shown by the 2.2- to 2.9-fold increases in steady-state concentrations of PAI-1 mRNA, and indicative of newly synthesized protein as shown by results in metabolic labeling experiments.. Our results are consistent with the hypothesis that precursors of insulin (proinsulin and proinsulin split products), known to be present in relatively high concentrations in plasma in patients with NIDDM and conditions characterized by insulin resistance, may directly stimulate PAI-1 synthesis, thereby attenuating fibrinolysis and accelerating atherogenesis.

Topics: Arteriosclerosis; C-Peptide; Culture Media; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Gene Expression; Humans; Liver; Plasminogen Activator Inhibitor 1; Proinsulin; Protein Precursors; Risk Factors; RNA, Messenger; Tumor Cells, Cultured

To identify characteristics of adult patients at baseline associated with duration of subsequent, continuous, subcutaneous infusion of insulin treatment (pump therapy) of type I diabetes.. For 6 wk, patients followed a standardized conventional therapy and kept a record of insulin dosages, capillary blood glucose concentrations, and symptomatic hypoglycemia. They were then hospitalized. Additional baseline data were obtained and pump therapy was started. Survival analysis was used to determine the relationship between baseline independent variables or risk factors and duration of pump therapy, which is the dependent variable.. Of the 68 participants, 33 (49%) terminated pump therapy after an average of 9.9 mo of treatment. Two models (each P < 0.00005) were developed that exhibited a high degree of consistency. Of the 6 variables, 5 were common to both models (HbA1, autonomic neuropathy, mean amplitude of glycemic excursions, frequency of symptoms of hypoglycemia when blood glucose was < 70 mg/dl, and erythema at injection sites). The sixth variable in model 1 (insulin dosage) was replaced in model 2 by a variable, Adult Self-Efficacy for Diabetes, which was obtained on the 33 more recently enrolled patients; this variable related to patient perceptions of self-care behaviors.. We found that, at baseline, the presence of a high concentration of HbA1 and a low estimation by the patient of their ability to treat the disease portend failure of insulin pump therapy as evidenced by its discontinuation. This effect is accentuated when clinical evidence of autonomic neuropathy is observed. These findings offer guidance in selecting patients with type I diabetes for insulin pump therapy.

Topics: Adolescent; Adult; Analysis of Variance; Blood Glucose; C-Peptide; Depression; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Diabetic Neuropathies; Female; Glycated Hemoglobin; Humans; Insulin; Insulin Infusion Systems; Male; Middle Aged; Prospective Studies; Radioimmunoassay; Risk Factors; Surveys and Questionnaires; Time Factors

We examined the impact of hypertension and microalbuminuria on insulin sensitivity in patients with Type 2 (non-insulin-dependent) diabetes mellitus using the euglycaemic insulin clamp technique in 52 Type 2 diabetic patients and in 19 healthy control subjects. Twenty-five diabetic patients had hypertension and 19 had microalbuminuria. Hypertension per se was associated with a 27% reduction in the rate of total glucose metabolism and a 40% reduction in the rate of non-oxidative glucose metabolism compared with normotensive Type 2 diabetic patients (both p < 0.001). Glucose metabolism was also impaired in normotensive microalbuminuric patients compared with normotensive normoalbuminuric patients (29.4 +/- 2.2 vs 40.5 +/- 2.8 mumol.kg lean body mass-1.min-1; p = 0.012), primarily due to a reduction in non-oxidative glucose metabolism (12.7 +/- 2.9 vs 21.1 +/- 2.6 mumol.kg lean body mass-1.min-1; p = 0.06). In a factorial ANOVA design, however, only hypertension (p = 0.008) and the combination of hypertension and microalbuminuria (p = 0.030) were significantly associated with the rate of glucose metabolism. The highest triglyceride and lowest HDL cholesterol concentrations were observed in Type 2 diabetic patients with both hypertension and microalbuminuria. Of note, glucose metabolism was indistinguishable from that in control subjects in Type 2 diabetic patients without hypertension and microalbuminuria (40.5 +/- 2.8 vs 44.4 +/- 2.8 mumol.kg lean body mass-1.min-1). We conclude that insulin resistance in Type 2 diabetes is predominantly associated with either hypertension or microalbuminuria or with both.

Topics: Albuminuria; Blood Glucose; Blood Pressure; Body Mass Index; C-Peptide; Cholesterol; Cholesterol, HDL; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Fasting; Fatty Acids, Nonesterified; Glucagon; Glucose; Glycated Hemoglobin; Humans; Hypertension; Insulin; Insulin Resistance; Lipids; Liver; Middle Aged; Reference Values; Triglycerides

To determine hemostasis variables in type I diabetic patients without clinically demonstrable micro- and macroangiopathy and to relate them to glycemic control.. Fifty patients and 50 comparable control subjects were enrolled in this study. The patients were subdivided in two groups, according to their level of HbA1c (group 1, n = 30, HbA1c < or = 8%; group 2, n = 20, HbA1c > 8%). We determined the platelet count, the platelet aggregation in the spontaneous state and in the presence of ADP or collagen, beta-thromboglobulin, platelet factor 4, fibrinogen, von Willebrand factor (factors VIII:C, VIIIR:Ag, and VIIIR:VW), plasma and urinary fibrinopeptide A, euglobulin lysis time, anticoagulant proteins C and S, and plasma viscosity.. All coagulation variables were significantly higher in diabetic patients compared with control subjects. Moreover, when the patients were subdivided according to their levels of HbA1c, the hemostatic disturbances appeared significantly more pronounced in the poorly controlled than in the well-controlled subjects.. This study confirms the existence of a state of hypercoagulability in type I diabetes. This hypercoagulability may be related to poor glycemic control. Our study suggests that the hemostasis disturbances precede demonstrable vascular complications.

Topics: Adenosine Diphosphate; Adult; Blood Coagulation Factors; Blood Pressure; Blood Viscosity; C-Peptide; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Collagen; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Female; Fibrinogen; Glycated Hemoglobin; Hemostasis; Humans; Male; Platelet Aggregation; Platelet Count; Reference Values; Triglycerides

Topics: Albuminuria; Blood Glucose; Blood Pressure; C-Peptide; Cholesterol; Coronary Disease; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Glycated Hemoglobin; Humans; Hyperinsulinism; Triglycerides

In 60 patients divided in three groups, each of 10 non-diabetic patients with essential hypertension (h) and of 10 hypertensive type 2 (non-insulin-dependent) diabetics (h+c), aged 31-63 years, the effect of 2-week treatment with nifedipine, captopril and prazosin on glycaemia, serum insulin (IRI) and C peptide (CP) after oral and i.v. glucose loading was compared. Nifedipine resulted in higher glycaemia levels in the oral test in both groups. This drug caused in group (h), but not in group (h+c), reduction of the glucose-dependent early increases of serum IRI and CP, more marked in respect to CP, what was expressed by the decrease of the serum CP:IRI ratio. These results prove that in non-diabetic patients nifedipine reduces the early response of the B-cells to glucose, but this effect is partly compensated by decreased insulin uptake by the liver. In patients with type 2 diabetes this phenomenon has not become manifest because of absence or reduction of early glucose-dependent insulin release. After captopril in both groups lower values of glycaemia and serum IRI and CP were found. Prazosin did not change the determined blood parameters.. nifedipine, captopril, prazosin have a small influence on secretory function of pancreatic B-cells and may be recommended for the treatment of hypertension in patients with type 2 (non-insulin-dependent) diabetes.

Topics: Adult; Antihypertensive Agents; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Humans; Hypertension; Insulin; Male; Middle Aged

The influence of albuminuria and proliferative retinopathy on concentration of serum lipoprotein (a) was examined cross-sectionally in 90 Type 1 diabetic patients. Concentrations of lipoprotein (a) were less in those with normoalbuminuria (90 (8-882) (median (range] U l-1) than in those with micro- or macro-albuminuria (137 (19-1722) U l-1, p less than 0.05). The prevalence of patients whose lipoprotein (a) concentrations were greater than 200 U l-1 was also greater (45% vs 24%, p = 0.03) among patients with albuminuria, but no difference was found between the microalbuminuric and macroalbuminuric groups (53 and 41%, respectively), or between those with or without proliferative retinopathy. The present finding that lipoprotein (a) concentrations may be increased at an early stage of diabetic renal disease may in part account for the excess ischaemic heart disease associated with diabetic nephropathy.

Topics: Albuminuria; Apolipoproteins B; Biomarkers; Blood Glucose; Blood Pressure; C-Peptide; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Coronary Disease; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Diabetic Retinopathy; Female; Glycated Hemoglobin; Humans; Lipoprotein(a); Lipoproteins; Male; Middle Aged; Triglycerides; Vascular Diseases

Recent data suggest genetic contributions to the microvascular complications of Type 1 (insulin-dependent) diabetes mellitus. Most research has focused on the HLA region, and the potential role of other genetic loci has not been adequately explored. We examined the possible relationship between DNA polymorphisms in the region 5' to the insulin gene on chromosome 11 and diabetic nephropathy. This was done by comparison of those diabetic patients homozygous for class 1 alleles at the 5' insulin gene polymorphism locus to 1/3 heterozygotes in a well-characterized series of 324 insulin-requiring diabetic patients from the Wisconsin Epidemiologic Study of Diabetic Retinopathy. Proteinuria (defined as greater than or equal to 0.3 g protein/l urine), was used as suggestive evidence for diabetic nephropathy. Hypertension, a frequent associated finding in diabetic patients with nephropathy, was defined as a blood pressure greater than 140/90 or a history of previous treatment of hypertension. The two genotypically defined groups did not differ from each other in regard to sex ratio, age at diagnosis, age at examination, duration of diabetes, body mass, HbAlc or C-peptide. The 1+1 group had a higher prevalence of proteinuria, 29% as compared to 16.2% in other genotypes (p less than 0.05). There was no significant difference in the frequency of hypertension between the two genotypic groups. This finding suggests that the 5' insulin gene polymorphism may be associated with risk for nephropathy, but the pathophysiologic mechanism remains unclear.

Topics: Blood Pressure; C-Peptide; Chromosome Mapping; Chromosomes, Human, Pair 11; Cohort Studies; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Diabetic Retinopathy; Female; Genes; Glycated Hemoglobin; Humans; Hypertension; Insulin; Male; Polymorphism, Genetic; Proteinuria; Sex Characteristics

Topics: C-Peptide; Coronary Disease; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Humans; Insulin

The effect of residual C-peptide secretion in longer standing IDDM on glycaemic control and the prevalence and evolution of complications over 2 years was evaluated. Thirty-one subjects with IDDM of 15.4 (1.5) years duration (mean SEM)) and residual C-peptide secretion, were matched for age, duration of diabetes and body mass index with 31 subjects without detectable C-peptide secretion. At trial entry and over 2 years, levels of HbA1, fructosamine and mean blood glucose were essentially similar in both groups. Levels of glycated albumin (GSA) were significantly higher in the C-peptide negative group after 3 and 9 months (P less than 0.05). An increased prevalence of proliferative retinopathy in the C-peptide negative group and of peripheral vascular disease in the C-peptide secretor group was apparent at entry to the study (both P less than 0.05), although no significant differences were observed after 1 or 2 years. There was no difference in the prevalence of peripheral or autonomic neuropathy, hypertension, nephropathy or ischaemic heart disease. Subjects with C-peptide concentrations greater than 0.100 pmol/ml at entry to this study had lower daily insulin requirements after 1 and 2 years, but behaved like the larger group with any detectable C-peptide secretion in all other respects. Residual C-peptide secretion was lost after 1 year in 7 patients, in whom glycaemic control during the year had been particularly poor. Insulin antibody titres were no different in the 2 groups at any time point. This study suggests that residual C-peptide secretion in longer standing IDDM confers the potential for limited improvements in glycaemic control. This effect appears to be insufficient to prevent the evolution of microvascular complications over a 2-year period. Residual C-peptide secretion and relative hyperinsulinaemia may be associated with an excess of peripheral vascular disease.

Topics: Adult; Albuminuria; Biomarkers; Blood Glucose; Blood Glucose Self-Monitoring; Blood Pressure; C-Peptide; Coronary Disease; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Diabetic Nephropathies; Diabetic Neuropathies; Diabetic Retinopathy; Follow-Up Studies; Fructosamine; Glycated Hemoglobin; Hexosamines; Humans; Hypertension; Middle Aged

The effects of enalapril treatment on blood glucose, insulin, and C-peptide levels and effects on the renin-angiotensin aldosterone system were studied in 22 hypertensive patients with non-insulin-dependent diabetes. After a 4-wk run-in period during which all previous antihypertensive drugs were discontinued, treatment was commenced with one daily dose of 10 mg enalapril. The dose was adjusted upward at 3-wk intervals to a maximum of 40 mg daily. In 3 subjects, addition of a thiazide diuretic was required after 9 wk of treatment. At completion of run-in and after 9 and 13 wk of treatment, subjects had blood samples drawn after fasting and 2 h after a standardized 1.6-mJ mixed meal. Mean fasting blood glucose at the end of the run-in period was 8.3 +/- 0.5 mM and at study completion was 7.3 +/- 0.4 mM. Mean postprandial blood glucose was 10.8 +/- 1.0 mM before treatment and 9.8 +/- 0.7 mM at study completion. The changes in fasting and postprandial blood glucose levels were not significant (P = .06 and P = .15, respectively). There was no significant change in glycosylated hemoglobin levels. Fasting and meal-stimulated insulin and C-peptide levels were not altered by enalapril treatment. Treatment was associated with a sustained reduction in plasma angiotensin-converting enzyme activity, an increase in plasma renin activity, reduced plasma aldosterone levels, and significant reductions in supine, seated, and standing arterial blood pressures.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Blood Glucose; Blood Pressure; C-Peptide; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Enalapril; Heart Rate; Humans; Hypertension; Insulin; Kallikreins; Renin; Renin-Angiotensin System

To investigate the hypothesis that insulin resistance is concerned in the pathogenesis of essential hypertension fasting glucose/insulin and fasting insulin/C-peptide ratios were measured in non-obese normotensive and hypertensive diabetic and non-diabetic subjects. Patients with essential hypertension had normal fasting serum insulin values and normal fasting glucose/insulin ratios; by contrast, the hypertensive non-insulin-dependent diabetic subjects had higher fasting serum insulin and lower glucose/insulin ratios than either normotensive diabetic or non-diabetic patients. Both hypertensive and normotensive diabetic subjects had higher fasting C-peptide values than those without diabetes. Hypertensive diabetic patients had the highest insulin/C-peptide ratios, indicating low hepatic insulin extraction rates. These findings suggest that hyperinsulinaemia is not causally related to essential hypertension but that it may contribute to the hypertension of non-insulin-dependent diabetes in association with low hepatic insulin clearance.

Topics: Analysis of Variance; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Humans; Hyperinsulinism; Hypertension; Insulin; Insulin Resistance; Male; Middle Aged

This study reports on the clinical pattern of 545 consecutive young diabetic patients with age at onset below 30 years attending a diabetes centre in Southern India. Three hundred and fourteen patients (57.7%) were classified as having non-insulin-dependent diabetes of the young (NIDDY), 119 (22%) as insulin-dependent diabetes (IDDM) and 28 (5%) as malnutrition-related diabetes (MRDM); 4% fibrocalculous pancreatic diabetes and 1% protein-deficient pancreatic diabetes. The remaining 84 patients could not be classified into any of the above categories. A positive family history of diabetes was more common in NIDDY compared to the other groups (P less than 0.001). While 40.3% of patients with IDDM had age at onset below 15 years, the other types of diabetes were rarely seen in patients younger than this. Body mass index (BMI) did not reliably indicate the MRDM forms of diabetes as 70% of patients with IDDM also had a BMI of less than 18, one of the criteria recommended for the diagnosis of MRDM. C-peptide levels in MRDM were intermediate between the IDDM and NIDDY groups. Microvascular complications were present in all the groups of young diabetics. The frequency was higher in NIDDY patients who also had a longer duration of diabetes. There was an increasing prevalence of complications with increasing duration of diabetes.

Topics: Adult; C-Peptide; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Glycated Hemoglobin; Humans; India; Male; Protein-Energy Malnutrition

The aim of the present study concerning patients with long-term insulin-dependent diabetes mellitus was to determine whether the serum lipid and lipoprotein concentrations differ in subjects with and without residual insulin secretion. We also investigated whether factors such as sex, smoking, physical activity and microvascular lesions were associated with particular lipoprotein profiles. C-peptide excretion (greater than or equal to 0.2 nmol) in 24-hour urine samples was used as an indicator of residual insulin secretion. Twenty-two pairs of patients with and without residual insulin secretion matched for age at onset and disease duration were participating in the investigations of glycaemic control and microvascular lesions. The HbA1c was significantly lower in C-peptide excretors than in the non-excretors (6.9 +/- 0.3 vs. 7.9 +/- 0.3%, p less than 0.025). The lipids and lipoprotein fractions were all within normal limits. The HDL2/3 ratio was significantly higher in C-peptide excretors than in non-excretors (1.72 +/- 0.28 vs. 1.10 +/- 0.09, p less than 0.05). Multiple regression analysis showed that factors, such as physical activity, body mass index and glycaemic control could explain more of the variation in the different lipid and lipoprotein fractions than residual C-peptide excretion alone. The only fraction correlating with C-peptide excretion was HDL3 cholesterol. It is concluded that minute residual insulin secretion per se is of minor importance for the regulation of lipids and lipoproteins. Glucose control and residual insulin secretion together with environmental factors seem to be of great importance for the regulation of the lipid and lipoprotein levels in insulin-dependent diabetes mellitus.

Topics: Alcohol Drinking; C-Peptide; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Female; Humans; Insulin; Insulin Secretion; Lipids; Lipoproteins; Male; Physical Exertion; Risk Factors; Smoking

We evaluated the long-term effects of indapamide, a non-thiazide diuretic, on blood pressure, glucoregulation, free insulin and C-peptide levels, and lipoprotein and apoprotein metabolism in 13 hypertensive diabetic patients for 24 weeks. Indapamide significantly reduced both systolic and diastolic blood pressure by 15% and 17%, respectively. Both mean fasting serum glucose and integrated glucose responses after oral glucose load (75 g) were significantly higher during indapamide therapy than at week 0. The mean fasting and stimulated C-peptide responses were significantly increased despite worsening glucose control. At the end of 24 weeks, mean glycosylated hemoglobin level had increased significantly. Indapamide caused a slight but insignificant rise in the total triglyceride, cholesterol, and low-density lipoprotein cholesterol levels, while the high-density lipoprotein cholesterol level decreased. In addition, the apoprotein A-1 concentrations remained unchanged while the apoprotein B-100 level decreased. Apart from hypokalemia (less than 3.5 mEq/L [less than 3.5 mmol/L]) in three patients that required oral potassium supplementation, biochemical changes were of no clinical consequence.

Topics: Adult; Aged; Apoproteins; Blood Glucose; C-Peptide; Diabetic Angiopathies; Diuretics; Female; Glycated Hemoglobin; Humans; Hypertension; Indapamide; Lipoproteins; Male; Middle Aged; Time Factors

The prevalence of macro- and microvascular disease and the distribution of glycosylated hemoglobin (Hb A1) were assessed in a representative Danish diabetes population living on the island of Falster with a population of 44.498 inhabitants. The diabetes population consisted of 533 diabetics of whom 166 were insulin-dependent (type I) and 367 non-insulin-dependent (type II). Among the 533 diabetics macrovascular complications as evidenced by myocardial infarction, gangrene or amputations and cerebrovascular catastrophes were present in 8%, 5% and 7%, respectively, while microvascular disease as evidenced by diabetic retinopathy was present in 53% of the cases. Multilogistic analysis showed no relationship between the macrovascular complications and the level of Hb A1, whereas there was a highly significant correlation between the level of Hb A1 and the presence of retinopathy in both patients with type I (P less than 0.01) and type II diabetes (P less than 0.001). The results emphasize the contention that the development of microvascular disease depends on the quality of blood glucose control while that of macrovascular disease seems unrelated to long-term hyperglycemia.

Topics: Blood Glucose; C-Peptide; Denmark; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Glycated Hemoglobin; Humans; Insulin; Male; Time Factors

The results of the study of immunoreactive insulin (IRI) and anti-insular hormones show their correlation with hemorheological disorders in patients with diabetic angiopathies. The results obtained indicate a possible involvement of the anti-insular hormones in the development of vascular changes in diabetes mellitus.

Topics: Adolescent; Adult; Aged; Blood Flow Velocity; Blood Viscosity; C-Peptide; Diabetic Angiopathies; Glucagon; Humans; Hydrocortisone; Insulin; Insulin Secretion; Middle Aged; Radioimmunoassay; Thyrotropin

Combined examination of 117 patients with insulin-dependent diabetes mellitus revealed the clinical and hormonal features of stable and labile diseases. Emphasis is laid on the complexity of the lability phenomenon; evidence is given for the necessity of differentiating between genuine lability and that of the iatrogenic type. The importance of hormonal shifts (depletion of the secretory capability of the insulin-producing apparatus and reduction of contrainsular effects) for the origin of destabilization of glucose homeostasis is discussed.

Topics: Adolescent; Adult; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Glucose Tolerance Test; Homeostasis; Humans; Insulin; Insulin Antibodies; Male; Middle Aged; Thyroid Hormones; Time Factors

Topics: Aldosterone; C-Peptide; Circadian Rhythm; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Homeostasis; Humans; Insulin Antibodies; Osmolar Concentration; Pregnancy; Pregnancy in Diabetics; Water-Electrolyte Balance

Decidual and intramyometrial spiral arteries from 18 insulin-dependent diabetic and 18 non-diabetic women were compared histologically. All women were normotensive and none had signs of pre-eclampsia. None of the infants in either group had intra-uterine growth retardation. Metabolic control in the diabetic women was assessed by pregnancy glucose level from the last trimester of pregnancy and by C-peptide in amniotic fluid and cord blood as a measure of the fetal beta-cell function. The intramyometrial and decidual parts of the spiral artery were normal in the non-diabetic group. None of the diabetic patients showed pathological changes in the intramyometrial part of the spiral artery. Two of the 18 diabetic patients had pathological changes (intramural fibrosis) in the decidual portion of the spiral artery. These two women had signs of diabetic angiopathy (White's class D and F) and in one of them, the background diabetic retinopathy progressed markedly during pregnancy. The pregnancy glucose level was above normal (greater than 6.2 mM/l) in 3 of 18 diabetics. The C-peptide values in amniotic fluid and cord blood were above normal in 11 of 17 and in 5 of 17, respectively. Both patients with spiral artery lesions had pregnancy glucose levels in the upper range, 5.86 and 5.98 mM/l, respectively and the highest value of C-peptide in the amniotic fluid and cord blood, suggesting exaggerated fetal beta-cell function.

Topics: Adult; Amniotic Fluid; Arteries; Blood Glucose; C-Peptide; Decidua; Diabetic Angiopathies; Female; Humans; Infant, Newborn; Myometrium; Pregnancy; Pregnancy in Diabetics; Prognosis

HLA antigen studies indicate heterogeneity of allele of B locus and propedine factor based on racial differences, while confirming specificity of DR3-DR4 for IDDM. C-peptide reserve is indicative of some sparing of beta cell destruction due to pre-existing nutritional state with enzymatic modulations modifying ketosis in the atypical IDDM in North India. Specific diabetic vascular disease has lesser geographical predisposition though factors that promote its severity or restrain its progress are not well understood.

Topics: Adolescent; Adult; Age Factors; C-Peptide; Child; Child, Preschool; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetic Angiopathies; HLA Antigens; Humans; India

Topics: Adolescent; Adult; Aged; C-Peptide; Diabetic Angiopathies; Diabetic Retinopathy; Female; Humans; Islets of Langerhans; Male; Middle Aged; Peptides

Topics: Blood Coagulation Disorders; C-Peptide; Child; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Diabetic Ketoacidosis; Diabetic Retinopathy; Glucagon; Hemoglobin A; Humans; Insulin; Insulin Secretion

Topics: C-Peptide; Diabetes Mellitus; Diabetic Angiopathies; Diabetic Nephropathies; Hemoglobins; Humans